Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility

CRISPR–Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted cont...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Nature chemical biology Ročník 20; číslo 3; s. 333 - 343
Hlavní autori: Schmidheini, Lukas, Mathis, Nicolas, Marquart, Kim Fabiano, Rothgangl, Tanja, Kissling, Lucas, Böck, Desirée, Chanez, Christelle, Wang, Jingrui Priscilla, Jinek, Martin, Schwank, Gerald
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: New York Nature Publishing Group US 01.03.2024
Nature Publishing Group
Predmet:
631/154/152
631/92/469
Biochemical Engineering
Biochemistry
Biocompatibility
Bioorganic Chemistry
Cell Biology
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
CRISPR
CRISPR-Associated Protein 9 - genetics
CRISPR-Associated Protein 9 - metabolism
CRISPR-Cas Systems - genetics
Directed evolution
Editing
Evolution
Gene Editing
Genetic disorders
Genetic modification
Genome
Genome editing
Genomes
Mutation
Nuclease
Robustness
ISSN:1552-4450, 1552-4469, 1552-4469
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Abstract CRISPR–Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 ( Cj Cas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evo Cj Cas9, primarily recognizes N 4 AH and N 5 HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N 3 VRYAC PAM site. Moreover, evo Cj Cas9 exhibits higher nuclease activity than wild-type Cj Cas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed Sp Cas9 variants. Combined with deaminases or reverse transcriptases, evo Cj Cas9 enables robust base and prime editing, with the small size of evo Cj Cas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems. Through directed evolution, the PAM compatibility of the compact Cas9 variant Cj Cas9 was increased. Evolved Cj Cas9 shows higher nuclease activity at canonical and non-canonical sites and enables robust in vivo gene editing from single AAV vectors.
AbstractList CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 (CjCas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evoCjCas9, primarily recognizes N4AH and N5HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N3VRYAC PAM site. Moreover, evoCjCas9 exhibits higher nuclease activity than wild-type CjCas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed SpCas9 variants. Combined with deaminases or reverse transcriptases, evoCjCas9 enables robust base and prime editing, with the small size of evoCjCas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems.CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 (CjCas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evoCjCas9, primarily recognizes N4AH and N5HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N3VRYAC PAM site. Moreover, evoCjCas9 exhibits higher nuclease activity than wild-type CjCas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed SpCas9 variants. Combined with deaminases or reverse transcriptases, evoCjCas9 enables robust base and prime editing, with the small size of evoCjCas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems.
CRISPR–Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 ( Cj Cas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evo Cj Cas9, primarily recognizes N 4 AH and N 5 HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N 3 VRYAC PAM site. Moreover, evo Cj Cas9 exhibits higher nuclease activity than wild-type Cj Cas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed Sp Cas9 variants. Combined with deaminases or reverse transcriptases, evo Cj Cas9 enables robust base and prime editing, with the small size of evo Cj Cas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems. Through directed evolution, the PAM compatibility of the compact Cas9 variant Cj Cas9 was increased. Evolved Cj Cas9 shows higher nuclease activity at canonical and non-canonical sites and enables robust in vivo gene editing from single AAV vectors.
CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM) and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution (PACE) to broaden the PAM compatibility of CjCas9, the smallest Cas9 orthologue characterized to date. The identified variant, termed evoCjCas9, primarily recognizes N4AH and N5HA PAM sequences, which occur ten-fold more frequently in the genome than the canonical N3VRYAC PAM site. Moreover, evoCjCas9 exhibits higher nuclease activity than wild-type CjCas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed SpCas9 variants. Combined with deaminases or reverse transcriptases, evoCjCas9 enables robust base- and prime editing, with the small size of evoCjCas9 base editors allowing tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus (AAV) vector systems.
CRISPR–Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 (CjCas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evoCjCas9, primarily recognizes N4AH and N5HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N3VRYAC PAM site. Moreover, evoCjCas9 exhibits higher nuclease activity than wild-type CjCas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed SpCas9 variants. Combined with deaminases or reverse transcriptases, evoCjCas9 enables robust base and prime editing, with the small size of evoCjCas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems.Through directed evolution, the PAM compatibility of the compact Cas9 variant CjCas9 was increased. Evolved CjCas9 shows higher nuclease activity at canonical and non-canonical sites and enables robust in vivo gene editing from single AAV vectors.
CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their requirement for a protospacer adjacent motif (PAM), and in vivo delivery is challenging due to their large size. Here, we use phage-assisted continuous directed evolution to broaden the PAM compatibility of Campylobacter jejuni Cas9 (CjCas9), the smallest Cas9 ortholog characterized to date. The identified variant, termed evoCjCas9, primarily recognizes N AH and N HA PAM sequences, which occur tenfold more frequently in the genome than the canonical N VRYAC PAM site. Moreover, evoCjCas9 exhibits higher nuclease activity than wild-type CjCas9 on canonical PAMs, with editing rates comparable to commonly used PAM-relaxed SpCas9 variants. Combined with deaminases or reverse transcriptases, evoCjCas9 enables robust base and prime editing, with the small size of evoCjCas9 base editors allowing for tissue-specific installation of A-to-G or C-to-T transition mutations from single adeno-associated virus vector systems.
Author Mathis, Nicolas
Kissling, Lucas
Schmidheini, Lukas
Rothgangl, Tanja
Wang, Jingrui Priscilla
Jinek, Martin
Schwank, Gerald
Böck, Desirée
Marquart, Kim Fabiano
Chanez, Christelle
Author_xml – sequence: 1
  givenname: Lukas
  orcidid: 0000-0001-5993-9985
  surname: Schmidheini
  fullname: Schmidheini, Lukas
  organization: Institute of Pharmacology and Toxicology, University of Zurich, Institute of Molecular Health Sciences, ETH Zurich
– sequence: 2
  givenname: Nicolas
  orcidid: 0000-0002-4051-8344
  surname: Mathis
  fullname: Mathis, Nicolas
  organization: Institute of Pharmacology and Toxicology, University of Zurich
– sequence: 3
  givenname: Kim Fabiano
  orcidid: 0000-0001-7393-4398
  surname: Marquart
  fullname: Marquart, Kim Fabiano
  organization: Institute of Pharmacology and Toxicology, University of Zurich, Institute of Molecular Health Sciences, ETH Zurich
– sequence: 4
  givenname: Tanja
  orcidid: 0000-0001-7799-2413
  surname: Rothgangl
  fullname: Rothgangl, Tanja
  organization: Institute of Pharmacology and Toxicology, University of Zurich
– sequence: 5
  givenname: Lucas
  orcidid: 0000-0002-4989-0695
  surname: Kissling
  fullname: Kissling, Lucas
  organization: Institute of Pharmacology and Toxicology, University of Zurich
– sequence: 6
  givenname: Desirée
  orcidid: 0000-0001-8142-0629
  surname: Böck
  fullname: Böck, Desirée
  organization: Institute of Pharmacology and Toxicology, University of Zurich
– sequence: 7
  givenname: Christelle
  orcidid: 0000-0002-3432-4375
  surname: Chanez
  fullname: Chanez, Christelle
  organization: Department of Biochemistry, University of Zurich
– sequence: 8
  givenname: Jingrui Priscilla
  orcidid: 0009-0003-2317-5911
  surname: Wang
  fullname: Wang, Jingrui Priscilla
  organization: Institute of Pharmacology and Toxicology, University of Zurich
– sequence: 9
  givenname: Martin
  orcidid: 0000-0002-7601-210X
  surname: Jinek
  fullname: Jinek, Martin
  organization: Department of Biochemistry, University of Zurich
– sequence: 10
  givenname: Gerald
  orcidid: 0000-0003-0767-2953
  surname: Schwank
  fullname: Schwank, Gerald
  email: schwank@pharma.uzh.ch
  organization: Institute of Pharmacology and Toxicology, University of Zurich
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37735239$$D View this record in MEDLINE/PubMed
BookMark eNp9kUtrFTEYhoO02Iv-ARcScONmbO6ZbIQy2FaoKChuQyaTaXOYkxyTzGn775s69ahddJUP8rzf5X2PwF6IwQHwBqMPGNH2JDPMW9UgQhuEGZHN7QtwiDknDWNC7e1qjg7AUc4rhKgQuH0JDqiUlBOqDsHPLobiwxznDAefnC1ugG4bp7n4GGAcoYE2rjfGFtitOpMV3JrkTSjwxpdr2KdoBvjt9MtCFd_7yZe7V2B_NFN2rx_fY_D97NOP7qK5_Hr-uTu9bCyTrDSE2kEJSxhhdhS8H4jiVCGCCR8NtUg5JkcxVIg5KgxFsjXIGWlVz1tHj8HHpetm7tdusC6UZCa9SX5t0p2Oxuv_f4K_1ldxq6XAAktcG7x_bJDir9nlotc-WzdNJrjqiCataDGpBsuKvnuCruKcQj1OE0WrsdVzWqm3_260W-WP4RUgC2BTzDm5cYdgpB9S1Uuqug7Vv1PVt1XUPhFZX8xDQPUqPz0vpYs01znhyqW_az-jugcz4bfL
CitedBy_id crossref_primary_10_1016_j_omtn_2024_102366
crossref_primary_10_1038_s41596_025_01244_7
crossref_primary_10_3389_fgeed_2025_1533197
crossref_primary_10_1038_s41591_024_03466_w
crossref_primary_10_1089_crispr_2024_0018
crossref_primary_10_1038_s41580_023_00697_6
crossref_primary_10_1186_s12967_024_05957_3
crossref_primary_10_1038_s41467_024_49233_w
crossref_primary_10_3390_pharmaceutics16091197
crossref_primary_10_1038_s41467_024_46107_z
crossref_primary_10_1038_s41592_024_02418_z
crossref_primary_10_1007_s11248_024_00404_x
crossref_primary_10_1038_s41587_025_02675_z
crossref_primary_10_1016_j_ymthe_2025_03_057
crossref_primary_10_1146_annurev_chembioeng_100522_114706
crossref_primary_10_1002_biot_70052
crossref_primary_10_1016_j_ymthe_2025_03_026
crossref_primary_10_3390_fishes10020084
crossref_primary_10_1007_s11427_023_2566_8
crossref_primary_10_1089_hum_2024_043
crossref_primary_10_1016_j_heliyon_2024_e38588
crossref_primary_10_1038_s41592_024_02460_x
crossref_primary_10_1038_s43856_025_00933_4
crossref_primary_10_1126_science_adt5199
Cites_doi 10.1016/j.celrep.2020.108364
10.1038/sj.cgt.7700672
10.1038/s41467-018-04580-3
10.1016/j.ymthe.2020.07.009
10.1089/crispr.2021.0143
10.1182/blood-2013-10-534032
10.1016/j.cell.2015.09.038
10.1089/genbio.2022.0015
10.1038/s41586-021-04058-1
10.1186/1479-0556-6-13
10.1126/science.abe7106
10.1016/j.omtn.2017.04.013
10.1038/nbt.4172
10.1038/s41586-020-03086-7
10.1126/scitranslmed.abl9238
10.1016/j.molcel.2018.01.032
10.1126/science.1232033
10.1038/s41587-019-0032-3
10.1038/s41587-020-0412-8
10.1038/s41587-021-00933-4
10.1126/science.1231143
10.1016/j.molcel.2021.08.008
10.1038/s41551-019-0501-5
10.1038/nature24644
10.1038/nature26155
10.1016/j.molcel.2017.02.007
10.1038/s41467-021-25375-z
10.1038/s41580-019-0131-5
10.1038/s41593-019-0431-2
10.1016/j.molcel.2018.12.003
10.1038/s41467-020-19687-9
10.1038/s41591-018-0209-1
10.1038/s41586-021-03534-y
10.1038/nature09929
10.1038/mt.2010.308
10.1016/j.ymthe.2022.01.005
10.1038/nature14592
10.1038/s41587-020-0453-z
10.1038/s41587-022-01410-2
10.1038/ncomms9425
10.1038/nature17946
10.1074/jbc.M410077200
10.1126/science.1225829
10.1038/6981
10.1126/science.aba8853
10.1038/s42003-022-03149-7
10.1096/fj.201900476RR
10.1021/acschembio.7b00855
10.1038/s41467-020-18715-y
10.1038/s41587-020-0555-7
10.1126/sciadv.aaz4849
10.1038/nrd.2018.110
10.1038/s41551-022-00911-4
10.1016/j.omtn.2021.08.025
10.1002/cbic.201800707
10.1038/sj.gt.3301905
10.1038/s41586-019-1711-4
10.1038/ncomms14500
10.1016/j.celrep.2020.02.010
10.1038/s41596-020-00465-2
10.1038/nature14299
10.1038/s41596-020-00410-3
10.1038/s41467-020-20633-y
10.1038/s41592-021-01348-4
10.1093/nar/gkv601
10.1016/j.ymthe.2020.12.007
10.1371/journal.pbio.3000686
10.1038/s41587-020-0642-9
10.1038/s41587-022-01533-6
10.1038/s41587-022-01613-7
10.1152/ajprenal.00128.2002
ContentType Journal Article
Copyright The Author(s), under exclusive licence to Springer Nature America, Inc. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Copyright_xml – notice: The Author(s), under exclusive licence to Springer Nature America, Inc. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
– notice: 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7QL
7QP
7QR
7TK
7TM
7U9
7X7
7XB
88A
88E
88I
8AO
8FD
8FE
8FG
8FH
8FI
8FJ
8FK
ABJCF
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BGLVJ
BHPHI
BKSAR
C1K
CCPQU
D1I
DWQXO
FR3
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
KB.
LK8
M0S
M1P
M2P
M7N
M7P
P64
PCBAR
PDBOC
PHGZM
PHGZT
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
Q9U
RC3
7X8
5PM
DOI 10.1038/s41589-023-01427-x
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Chemoreception Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Virology and AIDS Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Biology Database (Alumni Edition)
Medical Database (Alumni Edition)
Science Database (Alumni Edition)
ProQuest Pharma Collection
Technology Research Database
ProQuest SciTech Collection
ProQuest Technology Collection
ProQuest Natural Science Collection
ProQuest Hospital Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
Materials Science & Engineering Collection
ProQuest Central (Alumni Edition)
ProQuest One Sustainability
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Technology Collection
Natural Science Collection
Earth, Atmospheric & Aquatic Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Materials Science Collection
ProQuest Central Korea
Engineering Research Database
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Materials Science Database
ProQuest Biological Science Collection
Health & Medical Collection (Alumni Edition)
Medical Database
Science Database
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biological Science Database
Biotechnology and BioEngineering Abstracts
Earth, Atmospheric & Aquatic Science Database
Materials Science Collection
ProQuest Central Premium
ProQuest One Academic (New)
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic (retired)
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest Central Basic
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
ProQuest Central Student
ProQuest Central Essentials
Nucleic Acids Abstracts
SciTech Premium Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
Health Research Premium Collection
Natural Science Collection
Health & Medical Research Collection
Biological Science Collection
Chemoreception Abstracts
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Science Journals (Alumni Edition)
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
Earth, Atmospheric & Aquatic Science Database
ProQuest Hospital Collection
ProQuest Technology Collection
Health Research Premium Collection (Alumni)
Biological Science Database
Neurosciences Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
Engineering Research Database
ProQuest One Academic
Calcium & Calcified Tissue Abstracts
ProQuest One Academic (New)
Technology Collection
Technology Research Database
ProQuest One Academic Middle East (New)
Materials Science Collection
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Pharma Collection
ProQuest Biology Journals (Alumni Edition)
ProQuest Central
Earth, Atmospheric & Aquatic Science Collection
ProQuest Health & Medical Research Collection
Genetics Abstracts
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
Materials Science Database
ProQuest Materials Science Collection
ProQuest Central Basic
ProQuest Science Journals
ProQuest SciTech Collection
ProQuest Medical Library
Materials Science & Engineering Collection
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic


ProQuest Central Student
MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Anatomy & Physiology
Chemistry
EISSN 1552-4469
EndPage 343
ExternalDocumentID PMC7616171
37735239
10_1038_s41589_023_01427_x
Genre Journal Article
GrantInformation_xml – fundername: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
  grantid: 180257
  funderid: https://doi.org/10.13039/501100001711
– fundername: Swiss National Science Foundation
  grantid: 185293
– fundername: Swiss National Science Foundation
  grantid: 182567
– fundername: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
  grantid: 180257
GroupedDBID ---
0R~
123
29M
39C
3V.
4.4
53G
5BI
70F
7X7
88A
88E
88I
8AO
8FE
8FG
8FH
8FI
8FJ
8R4
8R5
AAEEF
AARCD
AAYZH
AAZLF
ABAWZ
ABDBF
ABJCF
ABJNI
ABLJU
ABUWG
ACBWK
ACGFS
ACGOD
ACIWK
ACPRK
ACUHS
ADBBV
AENEX
AEUYN
AFANA
AFBBN
AFKRA
AFRAH
AFSHS
AGAYW
AGHTU
AHBCP
AHMBA
AHOSX
AHSBF
AIBTJ
ALFFA
ALIPV
ALMA_UNASSIGNED_HOLDINGS
ARMCB
ASPBG
AVWKF
AXYYD
AZFZN
AZQEC
BBNVY
BENPR
BGLVJ
BHPHI
BKKNO
BKSAR
BPHCQ
BVXVI
CCPQU
CS3
CZ9
D1I
DB5
DU5
DWQXO
EBS
EE.
EJD
EMOBN
ESX
EXGXG
F5P
FEDTE
FQGFK
FSGXE
FYUFA
GNUQQ
HCIFZ
HMCUK
HVGLF
HZ~
KB.
KC.
LK5
LK8
M0L
M1P
M2P
M7P
M7R
NACWA
NNMJJ
O9-
ODYON
P2P
PCBAR
PDBOC
PQQKQ
PROAC
PSQYO
Q2X
RNT
RNTTT
SHXYY
SIXXV
SJN
SNYQT
SOJ
SV3
TAOOD
TBHMF
TDRGL
TSG
TUS
UKHRP
~8M
AAYXX
ABFSG
ACSTC
AEZWR
AFFHD
AFHIU
AGSTI
AHWEU
AIXLP
ALPWD
ATHPR
CITATION
NFIDA
PHGZM
PHGZT
PJZUB
PPXIY
PQGLB
ADXHL
CGR
CUY
CVF
ECM
EIF
NPM
PUEGO
7QL
7QP
7QR
7TK
7TM
7U9
7XB
8FD
8FK
C1K
FR3
H94
K9.
M7N
P64
PKEHL
PQEST
PQUKI
PRINS
Q9U
RC3
7X8
5PM
ID FETCH-LOGICAL-c474t-23cd96c2424cf65bd2953902125fa3c09e47f6dcd94e36a3078a0ea7c9b58e3
IEDL.DBID M7P
ISICitedReferencesCount 28
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001071113100001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1552-4450
1552-4469
IngestDate Tue Nov 04 02:05:35 EST 2025
Thu Oct 02 14:32:01 EDT 2025
Mon Oct 06 17:02:10 EDT 2025
Fri Sep 19 01:51:00 EDT 2025
Tue Nov 18 22:20:35 EST 2025
Sat Nov 29 02:45:22 EST 2025
Fri Feb 21 02:39:36 EST 2025
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 3
Language English
License 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c474t-23cd96c2424cf65bd2953902125fa3c09e47f6dcd94e36a3078a0ea7c9b58e3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0000-0001-7393-4398
0000-0002-3432-4375
0000-0002-4989-0695
0009-0003-2317-5911
0000-0002-7601-210X
0000-0003-0767-2953
0000-0001-5993-9985
0000-0002-4051-8344
0000-0001-7799-2413
0000-0001-8142-0629
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/7616171
PMID 37735239
PQID 2933664463
PQPubID 29034
PageCount 11
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_7616171
proquest_miscellaneous_2868120237
proquest_journals_2933664463
pubmed_primary_37735239
crossref_primary_10_1038_s41589_023_01427_x
crossref_citationtrail_10_1038_s41589_023_01427_x
springer_journals_10_1038_s41589_023_01427_x
PublicationCentury 2000
PublicationDate 2024-03-01
PublicationDateYYYYMMDD 2024-03-01
PublicationDate_xml – month: 03
  year: 2024
  text: 2024-03-01
  day: 01
PublicationDecade 2020
PublicationPlace New York
PublicationPlace_xml – name: New York
– name: United States
– name: Cambridge
PublicationTitle Nature chemical biology
PublicationTitleAbbrev Nat Chem Biol
PublicationTitleAlternate Nat Chem Biol
PublicationYear 2024
Publisher Nature Publishing Group US
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group US
– name: Nature Publishing Group
References Nair (CR51) 2014; 123
Yeh, Chiang, Rees, Edge, Liu (CR8) 2018; 9
Hu (CR37) 2020; 18
Koblan (CR47) 2018; 36
Sahng, Moon, Horton (CR53) 2004; 279
Nguyen Tran (CR61) 2020; 11
Dugar (CR58) 2018; 69
Mali (CR10) 2013; 339
Komor, Kim, Packer, Zuris, Liu (CR6) 2016; 533
Zetsche (CR2) 2015; 163
Gonçalves (CR66) 2011; 19
Walton, Christie, Whittaker, Kleinstiver (CR36) 2020; 368
Pacak, Sakai, Thattaliyath, Mah, Byrne (CR65) 2008; 6
Ran (CR3) 2015; 520
Lazzarotto (CR44) 2020; 38
Walton, Hsu, Joung, Kleinstiver (CR33) 2021; 16
Karvelis (CR40) 2021; 599
CR48
Rothgangl (CR18) 2021; 39
Zheng (CR15) 2022; 30
Zhang (CR21) 2022; 1
Miller (CR31) 2020; 38
Legut (CR42) 2020; 30
Jiao (CR59) 2021; 372
Villiger (CR50) 2021; 26
Zurek, Knyphausen, Neufeld, Pushpanath, Hollfelder (CR68) 2020; 11
Pu, Disare, Dickinson (CR26) 2019; 20
Nakagawa (CR34) 2022; 5
Xu (CR39) 2021; 81
Chen (CR22) 2022; 5
Kleinstiver (CR38) 2015; 523
Deverman, Ravina, Bankiewicz, Paul, Sah (CR12) 2018; 17
Clement (CR71) 2019; 37
Davis (CR20) 2022; 6
Kügler, Kilic, Bähr (CR55) 2003; 10
Yamada (CR30) 2017; 65
Miller, Wang, Liu (CR25) 2020; 15
Badran, Liu (CR28) 2015; 6
Zhu (CR62) 2004; 11
Jinek (CR1) 2012; 337
Mendell (CR13) 2021; 29
Collias, Beisel (CR43) 2021; 12
Levy (CR14) 2020; 4
Böck (CR19) 2022; 14
CR56
Musunuru (CR54) 2021; 593
Richter (CR45) 2020; 38
Hu (CR23) 2018; 556
Edraki (CR41) 2019; 73
Esvelt, Carlson, Liu (CR24) 2011; 472
Grisch-Chan (CR52) 2017; 7
Gaudelli (CR5) 2017; 551
Koblan (CR11) 2021; 589
Anzalone (CR7) 2019; 576
Morales, Gambhir, Bennett, Stedman (CR57) 2020; 28
Marquart (CR49) 2021; 12
Villiger (CR17) 2018; 24
Düring (CR70) 2020; 33
Saha (CR60) 2020; 6
Cong (CR9) 2013; 339
DeBenedictis (CR27) 2022; 19
Huang (CR32) 2023; 41
Li, Eastman, Schwartz, Draghia-Akli (CR67) 1999; 17
Liu (CR46) 2019; 33
Mir, Edraki, Lee, Sontheimer (CR35) 2018; 13
CR69
CR64
Kim (CR29) 2017; 8
Truong (CR16) 2015; 43
Jüttner (CR63) 2019; 22
Pickar-Oliver, Gersbach (CR4) 2019; 20
R Nakagawa (1427_CR34) 2022; 5
1427_CR56
AH Badran (1427_CR28) 2015; 6
JH Hu (1427_CR23) 2018; 556
SM Miller (1427_CR25) 2020; 15
A Edraki (1427_CR41) 2019; 73
N Nair (1427_CR51) 2014; 123
C Zheng (1427_CR15) 2022; 30
K Clement (1427_CR71) 2019; 37
C Saha (1427_CR60) 2020; 6
P Mali (1427_CR10) 2013; 339
BE Deverman (1427_CR12) 2018; 17
KF Marquart (1427_CR49) 2021; 12
H Zhang (1427_CR21) 2022; 1
T Karvelis (1427_CR40) 2021; 599
RT Walton (1427_CR36) 2020; 368
AC Komor (1427_CR6) 2016; 533
J Pu (1427_CR26) 2019; 20
LW Koblan (1427_CR11) 2021; 589
1427_CR64
WH Yeh (1427_CR8) 2018; 9
D-JJ Truong (1427_CR16) 2015; 43
HM Grisch-Chan (1427_CR52) 2017; 7
L Villiger (1427_CR50) 2021; 26
1427_CR69
KM Esvelt (1427_CR24) 2011; 472
JM Levy (1427_CR14) 2020; 4
M Jinek (1427_CR1) 2012; 337
DN Düring (1427_CR70) 2020; 33
M Yamada (1427_CR30) 2017; 65
SM Miller (1427_CR31) 2020; 38
CR Lazzarotto (1427_CR44) 2020; 38
TP Huang (1427_CR32) 2023; 41
FA Ran (1427_CR3) 2015; 520
NMM Gaudelli (1427_CR5) 2017; 551
MT Nguyen Tran (1427_CR61) 2020; 11
T Rothgangl (1427_CR18) 2021; 39
MF Richter (1427_CR45) 2020; 38
JR Mendell (1427_CR13) 2021; 29
Z Hu (1427_CR37) 2020; 18
A Pickar-Oliver (1427_CR4) 2019; 20
M Legut (1427_CR42) 2020; 30
AV Anzalone (1427_CR7) 2019; 576
C Jiao (1427_CR59) 2021; 372
PJ Zurek (1427_CR68) 2020; 11
Z Liu (1427_CR46) 2019; 33
B Zetsche (1427_CR2) 2015; 163
S Chen (1427_CR22) 2022; 5
LW Koblan (1427_CR47) 2018; 36
J Jüttner (1427_CR63) 2019; 22
MAFV Gonçalves (1427_CR66) 2011; 19
RT Walton (1427_CR33) 2021; 16
BP Kleinstiver (1427_CR38) 2015; 523
G Dugar (1427_CR58) 2018; 69
D Collias (1427_CR43) 2021; 12
K Musunuru (1427_CR54) 2021; 593
JR Davis (1427_CR20) 2022; 6
S Kügler (1427_CR55) 2003; 10
A Mir (1427_CR35) 2018; 13
HJ Zhu (1427_CR62) 2004; 11
L Villiger (1427_CR17) 2018; 24
X Li (1427_CR67) 1999; 17
EA DeBenedictis (1427_CR27) 2022; 19
X Xu (1427_CR39) 2021; 81
1427_CR48
WP Sahng (1427_CR53) 2004; 279
E Kim (1427_CR29) 2017; 8
D Böck (1427_CR19) 2022; 14
CA Pacak (1427_CR65) 2008; 6
L Cong (1427_CR9) 2013; 339
L Morales (1427_CR57) 2020; 28
References_xml – volume: 33
  start-page: 108364
  year: 2020
  ident: CR70
  article-title: Fast retrograde access to projection neuron circuits underlying vocal learning in songbirds
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2020.108364
– volume: 11
  start-page: 263
  year: 2004
  end-page: 272
  ident: CR62
  article-title: Cloning and analysis of human UroplakinII promoter and its application for gene therapy in bladder cancer
  publication-title: Cancer Gene Ther.
  doi: 10.1038/sj.cgt.7700672
– volume: 9
  start-page: 2184
  year: 2018
  ident: CR8
  article-title: In vivo base editing of post-mitotic sensory cells
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-04580-3
– volume: 28
  start-page: 1753
  year: 2020
  end-page: 1755
  ident: CR57
  article-title: Broader implications of progressive liver dysfunction and lethal sepsis in two boys following systemic high-dose AAV
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2020.07.009
– volume: 5
  start-page: 472
  year: 2022
  end-page: 486
  ident: CR22
  article-title: Compact 3Cas9 for efficient in vivo genome editing and adenine base editing
  publication-title: CRISPR J.
  doi: 10.1089/crispr.2021.0143
– volume: 123
  start-page: 3195
  year: 2014
  end-page: 3199
  ident: CR51
  article-title: Computationally designed liver-specific transcriptional modules and hyperactive factor IX improve hepatic gene therapy
  publication-title: Blood
  doi: 10.1182/blood-2013-10-534032
– volume: 163
  start-page: 759
  year: 2015
  end-page: 771
  ident: CR2
  article-title: Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR–Cas system
  publication-title: Cell
  doi: 10.1016/j.cell.2015.09.038
– volume: 1
  start-page: 285
  year: 2022
  end-page: 299
  ident: CR21
  article-title: Adenine base editing in vivo with a single adeno-associated virus vector
  publication-title: GEN Biotechnol.
  doi: 10.1089/genbio.2022.0015
– volume: 599
  start-page: 692
  year: 2021
  end-page: 696
  ident: CR40
  article-title: Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
  publication-title: Nature
  doi: 10.1038/s41586-021-04058-1
– volume: 6
  year: 2008
  ident: CR65
  article-title: Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice
  publication-title: Genet. Vaccines Ther.
  doi: 10.1186/1479-0556-6-13
– volume: 372
  start-page: 941
  year: 2021
  end-page: 948
  ident: CR59
  article-title: Noncanonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9
  publication-title: Science
  doi: 10.1126/science.abe7106
– volume: 7
  start-page: 339
  year: 2017
  end-page: 349
  ident: CR52
  article-title: Low-dose gene therapy for murine PKU using episomal naked DNA vectors expressing PAH from its endogenous liver promoter
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1016/j.omtn.2017.04.013
– volume: 36
  start-page: 843
  year: 2018
  end-page: 848
  ident: CR47
  article-title: Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.4172
– volume: 589
  start-page: 608
  year: 2021
  end-page: 614
  ident: CR11
  article-title: In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice
  publication-title: Nature
  doi: 10.1038/s41586-020-03086-7
– volume: 14
  start-page: 9238
  year: 2022
  ident: CR19
  article-title: In vivo prime editing of a metabolic liver disease in mice
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.abl9238
– volume: 69
  start-page: 893
  year: 2018
  end-page: 905
  ident: CR58
  article-title: CRISPR RNA-dependent binding and cleavage of endogenous RNAs by the Cas9
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2018.01.032
– volume: 339
  start-page: 823
  year: 2013
  end-page: 826
  ident: CR10
  article-title: RNA-guided human genome engineering via Cas9
  publication-title: Science
  doi: 10.1126/science.1232033
– volume: 37
  start-page: 224
  year: 2019
  end-page: 226
  ident: CR71
  article-title: CRISPResso2 provides accurate and rapid genome editing sequence analysis
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-019-0032-3
– volume: 38
  start-page: 471
  year: 2020
  end-page: 481
  ident: CR31
  article-title: Continuous evolution of Cas9 variants compatible with non-G PAMs
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0412-8
– volume: 39
  start-page: 949
  year: 2021
  end-page: 957
  ident: CR18
  article-title: In vivo adenine base editing of in macaques reduces LDL cholesterol levels
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-021-00933-4
– volume: 339
  start-page: 819
  year: 2013
  end-page: 823
  ident: CR9
  article-title: Multiplex genome engineering using CRISPR/Cas systems
  publication-title: Science
  doi: 10.1126/science.1231143
– volume: 81
  start-page: 4333
  year: 2021
  end-page: 4345
  ident: CR39
  article-title: Engineered miniature CRISPR–Cas system for mammalian genome regulation and editing
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2021.08.008
– volume: 4
  start-page: 97
  year: 2020
  end-page: 110
  ident: CR14
  article-title: Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses
  publication-title: Nat. Biomed. Eng.
  doi: 10.1038/s41551-019-0501-5
– volume: 551
  start-page: 464
  year: 2017
  end-page: 471
  ident: CR5
  article-title: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage
  publication-title: Nature
  doi: 10.1038/nature24644
– volume: 556
  start-page: 57
  year: 2018
  end-page: 63
  ident: CR23
  article-title: Evolved Cas9 variants with broad PAM compatibility and high DNA specificity
  publication-title: Nature
  doi: 10.1038/nature26155
– volume: 65
  start-page: 1109
  year: 2017
  end-page: 1121
  ident: CR30
  article-title: Crystal structure of the minimal Cas9 from reveals the molecular diversity in the CRISPR–Cas9 systems
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2017.02.007
– volume: 12
  start-page: 5114
  year: 2021
  ident: CR49
  article-title: Predicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-25375-z
– volume: 20
  start-page: 490
  year: 2019
  end-page: 507
  ident: CR4
  article-title: The next generation of CRISPR–Cas technologies and applications
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/s41580-019-0131-5
– volume: 22
  start-page: 1345
  year: 2019
  end-page: 1356
  ident: CR63
  article-title: Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates and humans
  publication-title: Nat. Neurosci.
  doi: 10.1038/s41593-019-0431-2
– volume: 73
  start-page: 714
  year: 2019
  end-page: 726
  ident: CR41
  article-title: A compact, high-accuracy Cas9 with a dinucleotide PAM for in vivo genome editing
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2018.12.003
– volume: 11
  start-page: 6023
  year: 2020
  ident: CR68
  article-title: UMI-linked consensus sequencing enables phylogenetic analysis of directed evolution
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-19687-9
– volume: 24
  start-page: 1519
  year: 2018
  end-page: 1525
  ident: CR17
  article-title: Treatment of a metabolic liver disease by in vivo genome base editing in adult mice
  publication-title: Nat. Med.
  doi: 10.1038/s41591-018-0209-1
– volume: 593
  start-page: 429
  year: 2021
  end-page: 434
  ident: CR54
  article-title: In vivo CRISPR base editing of durably lowers cholesterol in primates
  publication-title: Nature
  doi: 10.1038/s41586-021-03534-y
– volume: 472
  start-page: 499
  year: 2011
  end-page: 503
  ident: CR24
  article-title: A system for the continuous directed evolution of biomolecules
  publication-title: Nature
  doi: 10.1038/nature09929
– volume: 19
  start-page: 1331
  year: 2011
  end-page: 1341
  ident: CR66
  article-title: Transcription factor rational design improves directed differentiation of human mesenchymal stem cells into skeletal myocytes
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2010.308
– volume: 30
  start-page: 1343
  year: 2022
  end-page: 1351
  ident: CR15
  article-title: A flexible split prime editor using truncated reverse transcriptase improves dual-AAV delivery in mouse liver
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2022.01.005
– volume: 523
  start-page: 481
  year: 2015
  end-page: 485
  ident: CR38
  article-title: Engineered CRISPR–Cas9 nucleases with altered PAM specificities
  publication-title: Nature
  doi: 10.1038/nature14592
– volume: 38
  start-page: 883
  year: 2020
  end-page: 891
  ident: CR45
  article-title: Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0453-z
– ident: CR64
– volume: 41
  start-page: 96
  year: 2023
  end-page: 107
  ident: CR32
  article-title: High-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-022-01410-2
– volume: 6
  year: 2015
  ident: CR28
  article-title: Development of potent in vivo mutagenesis plasmids with broad mutational spectra
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms9425
– volume: 533
  start-page: 420
  year: 2016
  end-page: 424
  ident: CR6
  article-title: Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
  publication-title: Nature
  doi: 10.1038/nature17946
– volume: 279
  start-page: 50630
  year: 2004
  end-page: 50638
  ident: CR53
  article-title: Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M410077200
– volume: 337
  start-page: 816
  year: 2012
  end-page: 821
  ident: CR1
  article-title: A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity
  publication-title: Science
  doi: 10.1126/science.1225829
– volume: 17
  start-page: 241
  year: 1999
  end-page: 245
  ident: CR67
  article-title: Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences
  publication-title: Nat. Biotechnol.
  doi: 10.1038/6981
– volume: 368
  start-page: 290
  year: 2020
  end-page: 296
  ident: CR36
  article-title: Unconstrained genome targeting with near-PAMless engineered CRISPR–Cas9 variants
  publication-title: Science
  doi: 10.1126/science.aba8853
– volume: 5
  start-page: 211
  year: 2022
  ident: CR34
  article-title: Engineered Cas9 variant with enhanced activity and broader targeting range
  publication-title: Commun. Biol.
  doi: 10.1038/s42003-022-03149-7
– volume: 33
  start-page: 9210
  year: 2019
  end-page: 9219
  ident: CR46
  article-title: Improved base editor for efficient editing in GC contexts in rabbits with an optimized AID–Cas9 fusion
  publication-title: FASEB J.
  doi: 10.1096/fj.201900476RR
– volume: 13
  start-page: 357
  year: 2018
  end-page: 365
  ident: CR35
  article-title: Type II-C CRISPR–Cas9 biology, mechanism, and application
  publication-title: ACS Chem. Biol.
  doi: 10.1021/acschembio.7b00855
– volume: 11
  start-page: 4871
  year: 2020
  ident: CR61
  article-title: Engineering domain-inlaid Cas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-18715-y
– ident: CR56
– volume: 38
  start-page: 1317
  year: 2020
  end-page: 1327
  ident: CR44
  article-title: CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0555-7
– volume: 6
  start-page: 4849
  year: 2020
  end-page: 4866
  ident: CR60
  article-title: Guide-free Cas9 from pathogenic bacteria causes severe damage to DNA
  publication-title: Sci. Adv.
  doi: 10.1126/sciadv.aaz4849
– volume: 17
  start-page: 641
  year: 2018
  end-page: 659
  ident: CR12
  article-title: Gene therapy for neurological disorders: progress and prospects
  publication-title: Nat. Rev. Drug Discov.
  doi: 10.1038/nrd.2018.110
– volume: 6
  start-page: 1272
  year: 2022
  end-page: 1283
  ident: CR20
  article-title: Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors
  publication-title: Nat. Biomed. Eng.
  doi: 10.1038/s41551-022-00911-4
– volume: 26
  start-page: 502
  year: 2021
  end-page: 510
  ident: CR50
  article-title: Replacing the Cas9 HNH domain by deaminases generates compact base editors with an alternative targeting scope
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1016/j.omtn.2021.08.025
– ident: CR69
– volume: 20
  start-page: 1547
  year: 2019
  end-page: 1553
  ident: CR26
  article-title: Evolution of C-terminal modification tolerance in full-length and split T7 RNA polymerase biosensors
  publication-title: ChemBioChem
  doi: 10.1002/cbic.201800707
– volume: 10
  start-page: 337
  year: 2003
  end-page: 347
  ident: CR55
  article-title: Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area
  publication-title: Gene Ther.
  doi: 10.1038/sj.gt.3301905
– volume: 576
  start-page: 149
  year: 2019
  end-page: 157
  ident: CR7
  article-title: Search-and-replace genome editing without double-strand breaks or donor DNA
  publication-title: Nature
  doi: 10.1038/s41586-019-1711-4
– ident: CR48
– volume: 8
  start-page: 14500
  year: 2017
  ident: CR29
  article-title: In vivo genome editing with a small Cas9 orthologue derived from
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms14500
– volume: 30
  start-page: 2859
  year: 2020
  end-page: 2868
  ident: CR42
  article-title: High-throughput screens of PAM-flexible Cas9 variants for gene knockout and transcriptional modulation
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2020.02.010
– volume: 16
  start-page: 1511
  year: 2021
  end-page: 1547
  ident: CR33
  article-title: Scalable characterization of the PAM requirements of CRISPR–Cas enzymes using HT-PAMDA
  publication-title: Nat. Protoc.
  doi: 10.1038/s41596-020-00465-2
– volume: 520
  start-page: 186
  year: 2015
  end-page: 191
  ident: CR3
  article-title: In vivo genome editing using Cas9
  publication-title: Nature
  doi: 10.1038/nature14299
– volume: 15
  start-page: 4101
  year: 2020
  end-page: 4127
  ident: CR25
  article-title: Phage-assisted continuous and non-continuous evolution
  publication-title: Nat. Protoc.
  doi: 10.1038/s41596-020-00410-3
– volume: 12
  start-page: 555
  year: 2021
  ident: CR43
  article-title: CRISPR technologies and the search for the PAM-free nuclease
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-20633-y
– volume: 19
  start-page: 55
  year: 2022
  end-page: 64
  ident: CR27
  article-title: Systematic molecular evolution enables robust biomolecule discovery
  publication-title: Nat. Methods
  doi: 10.1038/s41592-021-01348-4
– volume: 43
  start-page: 6450
  year: 2015
  end-page: 6458
  ident: CR16
  article-title: Development of an intein-mediated split-Cas9 system for gene therapy
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkv601
– volume: 29
  start-page: 464
  year: 2021
  end-page: 488
  ident: CR13
  article-title: Current clinical applications of in vivo gene therapy with AAVs
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2020.12.007
– volume: 18
  start-page: e3000686
  year: 2020
  ident: CR37
  article-title: A compact Cas9 ortholog from ( Cas9) expands the DNA targeting scope
  publication-title: PLoS Biol.
  doi: 10.1371/journal.pbio.3000686
– volume: 576
  start-page: 149
  year: 2019
  ident: 1427_CR7
  publication-title: Nature
  doi: 10.1038/s41586-019-1711-4
– volume: 19
  start-page: 55
  year: 2022
  ident: 1427_CR27
  publication-title: Nat. Methods
  doi: 10.1038/s41592-021-01348-4
– volume: 339
  start-page: 823
  year: 2013
  ident: 1427_CR10
  publication-title: Science
  doi: 10.1126/science.1232033
– volume: 12
  start-page: 5114
  year: 2021
  ident: 1427_CR49
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-021-25375-z
– ident: 1427_CR56
  doi: 10.1038/s41587-020-0642-9
– volume: 28
  start-page: 1753
  year: 2020
  ident: 1427_CR57
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2020.07.009
– volume: 24
  start-page: 1519
  year: 2018
  ident: 1427_CR17
  publication-title: Nat. Med.
  doi: 10.1038/s41591-018-0209-1
– volume: 38
  start-page: 1317
  year: 2020
  ident: 1427_CR44
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0555-7
– ident: 1427_CR48
  doi: 10.1038/s41587-022-01533-6
– volume: 279
  start-page: 50630
  year: 2004
  ident: 1427_CR53
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M410077200
– volume: 69
  start-page: 893
  year: 2018
  ident: 1427_CR58
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2018.01.032
– volume: 39
  start-page: 949
  year: 2021
  ident: 1427_CR18
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-021-00933-4
– volume: 15
  start-page: 4101
  year: 2020
  ident: 1427_CR25
  publication-title: Nat. Protoc.
  doi: 10.1038/s41596-020-00410-3
– volume: 5
  start-page: 211
  year: 2022
  ident: 1427_CR34
  publication-title: Commun. Biol.
  doi: 10.1038/s42003-022-03149-7
– volume: 43
  start-page: 6450
  year: 2015
  ident: 1427_CR16
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkv601
– volume: 372
  start-page: 941
  year: 2021
  ident: 1427_CR59
  publication-title: Science
  doi: 10.1126/science.abe7106
– volume: 599
  start-page: 692
  year: 2021
  ident: 1427_CR40
  publication-title: Nature
  doi: 10.1038/s41586-021-04058-1
– volume: 6
  year: 2015
  ident: 1427_CR28
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms9425
– volume: 123
  start-page: 3195
  year: 2014
  ident: 1427_CR51
  publication-title: Blood
  doi: 10.1182/blood-2013-10-534032
– volume: 7
  start-page: 339
  year: 2017
  ident: 1427_CR52
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1016/j.omtn.2017.04.013
– volume: 16
  start-page: 1511
  year: 2021
  ident: 1427_CR33
  publication-title: Nat. Protoc.
  doi: 10.1038/s41596-020-00465-2
– volume: 20
  start-page: 490
  year: 2019
  ident: 1427_CR4
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/s41580-019-0131-5
– volume: 37
  start-page: 224
  year: 2019
  ident: 1427_CR71
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-019-0032-3
– volume: 36
  start-page: 843
  year: 2018
  ident: 1427_CR47
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.4172
– volume: 472
  start-page: 499
  year: 2011
  ident: 1427_CR24
  publication-title: Nature
  doi: 10.1038/nature09929
– volume: 41
  start-page: 96
  year: 2023
  ident: 1427_CR32
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-022-01410-2
– volume: 18
  start-page: e3000686
  year: 2020
  ident: 1427_CR37
  publication-title: PLoS Biol.
  doi: 10.1371/journal.pbio.3000686
– ident: 1427_CR69
  doi: 10.1038/s41587-022-01613-7
– volume: 29
  start-page: 464
  year: 2021
  ident: 1427_CR13
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2020.12.007
– volume: 589
  start-page: 608
  year: 2021
  ident: 1427_CR11
  publication-title: Nature
  doi: 10.1038/s41586-020-03086-7
– volume: 11
  start-page: 263
  year: 2004
  ident: 1427_CR62
  publication-title: Cancer Gene Ther.
  doi: 10.1038/sj.cgt.7700672
– volume: 17
  start-page: 241
  year: 1999
  ident: 1427_CR67
  publication-title: Nat. Biotechnol.
  doi: 10.1038/6981
– volume: 65
  start-page: 1109
  year: 2017
  ident: 1427_CR30
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2017.02.007
– volume: 6
  start-page: 4849
  year: 2020
  ident: 1427_CR60
  publication-title: Sci. Adv.
  doi: 10.1126/sciadv.aaz4849
– volume: 368
  start-page: 290
  year: 2020
  ident: 1427_CR36
  publication-title: Science
  doi: 10.1126/science.aba8853
– volume: 523
  start-page: 481
  year: 2015
  ident: 1427_CR38
  publication-title: Nature
  doi: 10.1038/nature14592
– volume: 6
  year: 2008
  ident: 1427_CR65
  publication-title: Genet. Vaccines Ther.
  doi: 10.1186/1479-0556-6-13
– ident: 1427_CR64
  doi: 10.1152/ajprenal.00128.2002
– volume: 9
  start-page: 2184
  year: 2018
  ident: 1427_CR8
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-018-04580-3
– volume: 33
  start-page: 9210
  year: 2019
  ident: 1427_CR46
  publication-title: FASEB J.
  doi: 10.1096/fj.201900476RR
– volume: 38
  start-page: 471
  year: 2020
  ident: 1427_CR31
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0412-8
– volume: 339
  start-page: 819
  year: 2013
  ident: 1427_CR9
  publication-title: Science
  doi: 10.1126/science.1231143
– volume: 30
  start-page: 2859
  year: 2020
  ident: 1427_CR42
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2020.02.010
– volume: 38
  start-page: 883
  year: 2020
  ident: 1427_CR45
  publication-title: Nat. Biotechnol.
  doi: 10.1038/s41587-020-0453-z
– volume: 19
  start-page: 1331
  year: 2011
  ident: 1427_CR66
  publication-title: Mol. Ther.
  doi: 10.1038/mt.2010.308
– volume: 337
  start-page: 816
  year: 2012
  ident: 1427_CR1
  publication-title: Science
  doi: 10.1126/science.1225829
– volume: 22
  start-page: 1345
  year: 2019
  ident: 1427_CR63
  publication-title: Nat. Neurosci.
  doi: 10.1038/s41593-019-0431-2
– volume: 533
  start-page: 420
  year: 2016
  ident: 1427_CR6
  publication-title: Nature
  doi: 10.1038/nature17946
– volume: 556
  start-page: 57
  year: 2018
  ident: 1427_CR23
  publication-title: Nature
  doi: 10.1038/nature26155
– volume: 14
  start-page: 9238
  year: 2022
  ident: 1427_CR19
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.abl9238
– volume: 10
  start-page: 337
  year: 2003
  ident: 1427_CR55
  publication-title: Gene Ther.
  doi: 10.1038/sj.gt.3301905
– volume: 1
  start-page: 285
  year: 2022
  ident: 1427_CR21
  publication-title: GEN Biotechnol.
  doi: 10.1089/genbio.2022.0015
– volume: 26
  start-page: 502
  year: 2021
  ident: 1427_CR50
  publication-title: Mol. Ther. Nucleic Acids
  doi: 10.1016/j.omtn.2021.08.025
– volume: 11
  start-page: 6023
  year: 2020
  ident: 1427_CR68
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-19687-9
– volume: 73
  start-page: 714
  year: 2019
  ident: 1427_CR41
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2018.12.003
– volume: 17
  start-page: 641
  year: 2018
  ident: 1427_CR12
  publication-title: Nat. Rev. Drug Discov.
  doi: 10.1038/nrd.2018.110
– volume: 30
  start-page: 1343
  year: 2022
  ident: 1427_CR15
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2022.01.005
– volume: 33
  start-page: 108364
  year: 2020
  ident: 1427_CR70
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2020.108364
– volume: 5
  start-page: 472
  year: 2022
  ident: 1427_CR22
  publication-title: CRISPR J.
  doi: 10.1089/crispr.2021.0143
– volume: 20
  start-page: 1547
  year: 2019
  ident: 1427_CR26
  publication-title: ChemBioChem
  doi: 10.1002/cbic.201800707
– volume: 13
  start-page: 357
  year: 2018
  ident: 1427_CR35
  publication-title: ACS Chem. Biol.
  doi: 10.1021/acschembio.7b00855
– volume: 11
  start-page: 4871
  year: 2020
  ident: 1427_CR61
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-18715-y
– volume: 81
  start-page: 4333
  year: 2021
  ident: 1427_CR39
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2021.08.008
– volume: 6
  start-page: 1272
  year: 2022
  ident: 1427_CR20
  publication-title: Nat. Biomed. Eng.
  doi: 10.1038/s41551-022-00911-4
– volume: 551
  start-page: 464
  year: 2017
  ident: 1427_CR5
  publication-title: Nature
  doi: 10.1038/nature24644
– volume: 8
  start-page: 14500
  year: 2017
  ident: 1427_CR29
  publication-title: Nat. Commun.
  doi: 10.1038/ncomms14500
– volume: 520
  start-page: 186
  year: 2015
  ident: 1427_CR3
  publication-title: Nature
  doi: 10.1038/nature14299
– volume: 4
  start-page: 97
  year: 2020
  ident: 1427_CR14
  publication-title: Nat. Biomed. Eng.
  doi: 10.1038/s41551-019-0501-5
– volume: 163
  start-page: 759
  year: 2015
  ident: 1427_CR2
  publication-title: Cell
  doi: 10.1016/j.cell.2015.09.038
– volume: 12
  start-page: 555
  year: 2021
  ident: 1427_CR43
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-20633-y
– volume: 593
  start-page: 429
  year: 2021
  ident: 1427_CR54
  publication-title: Nature
  doi: 10.1038/s41586-021-03534-y
SSID ssj0036618
Score 2.553964
Snippet CRISPR–Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their...
CRISPR-Cas9 genome engineering is a powerful technology for correcting genetic diseases. However, the targeting range of Cas9 proteins is limited by their...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 333
SubjectTerms 631/154/152
631/92/469
Biochemical Engineering
Biochemistry
Biocompatibility
Bioorganic Chemistry
Cell Biology
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
CRISPR
CRISPR-Associated Protein 9 - genetics
CRISPR-Associated Protein 9 - metabolism
CRISPR-Cas Systems - genetics
Directed evolution
Editing
Evolution
Gene Editing
Genetic disorders
Genetic modification
Genome
Genome editing
Genomes
Mutation
Nuclease
Robustness
Title Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility
URI https://link.springer.com/article/10.1038/s41589-023-01427-x
https://www.ncbi.nlm.nih.gov/pubmed/37735239
https://www.proquest.com/docview/2933664463
https://www.proquest.com/docview/2868120237
https://pubmed.ncbi.nlm.nih.gov/PMC7616171
Volume 20
WOSCitedRecordID wos001071113100001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVPQU
  databaseName: Biological Science Database
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: M7P
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: http://search.proquest.com/biologicalscijournals
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Earth, Atmospheric & Aquatic Science Database
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: PCBAR
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/eaasdb
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Health & Medicine (ProQuest)
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: 7X7
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/healthcomplete
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Materials Science Database
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: KB.
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: http://search.proquest.com/materialsscijournals
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: BENPR
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Science Database
  customDbUrl:
  eissn: 1552-4469
  dateEnd: 20241209
  omitProxy: false
  ssIdentifier: ssj0036618
  issn: 1552-4450
  databaseCode: M2P
  dateStart: 20230101
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/sciencejournals
  providerName: ProQuest
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3db9MwED-xDQle-Nj4CIzKSIgXMEtjJ7afUFdtQoJVESDUt8hxHFEEyWjSavvvOTtJpzKxF14iRbk4ce5yZ59__h3AqyTOteRjSXMmS8qLpKB5EklaljY0WqJXZn6j8Ccxm8n5XKV9wq3pYZWDT_SOuqiNy5EfYVhiCQbvhL0__01d1Si3utqX0NiBPceSwDx0Lx08Mcr7_J5jGaOcx2G_aSZk8qjBwOXAQpFDE_FI0IvtwHRttHkdNPnXyqkPSKf3_7crD-BePxQlk852HsItW-3DwaTCafivS_KaeHCoz7rvw53pUBjuAL45RqtFtapXDekioi2IXfc2TOqSaOKh7aYl0x9T3Siyxhk5qpC4rC_Jl7UuSDo566TaDp97-Qi-nJ58nX6gfXkGarjgLY2YKVRi3P4SU6LOi0jFTDnK-LjUzITKclEmBQpxyxKNzkTq0GphVB5Lyx7DblVX9ikQqbAJrbAJo3miczkutdKOhsiIPDIygPGgmcz0zOWugMbPzK-gM5l12sxQm5nXZnYRwJvNPecdb8eN0oeDprL-H26yKzUF8HJzGb-1W1LRlcWvnEXS8bdhSyKAJ519bB7HhMDRLVMBiC3L2Qg4Zu_tK9Xiu2f4Fombdo4DeDvY2NVr_bsXz27uxXO4i2_KOwDdIey2y5V9AbfNul00yxHsiLnwRzmCveOTWfoZzz4ev8PjWZSO_J_1B5pBJYY
linkProvider ProQuest
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwEB6VglQuPFoegQJGAi40ajZ2YueA0GqhatXtaiUq1BOW4zhiq5KUTXbp_id-JGMn2Wqp6K0Hzpk4Y-ebGT8-zwC8iaNUCdYTfkpF7rMszvw0DoWf5ybQSqBXpu6i8JCPRuLkJBmvwe_uLoylVXY-0TnqrNR2j3wXwxKNMXjH9OP5T99WjbKnq10JjQYWh2bxC5ds1YeDT_h_34bh3ufjwb7fVhXwNeOs9kOqsyTW9lqEzlHVLEwiXPijC49yRXWQGMbzOEMhZmis0AaECoziOkkjYSi2egtu4yQiFI4oOO78PmrndhNtTjOfsShor-gEVOxWGCYtNSm03CUWcv9iNQxemdtepWj-dU7rwt_e_f9r4B7AvXaaTfqNXTyENVNswla_UHX5Y0HeEUd8dScKm7Ax6IrebcFXm61rUszKWUWaaG8yYuatfZIyJ4o42r6uyeB0oKqEzBXacFETu6NN0mmpMjLuHzVSdcM9XjyCLzfQ18ewXpSFeQpEJNiESrAJrVisUtHLVaJsiiXN01ALD3odDqRus7Lb4iBn0rEDqJANdiRiRzrsyAsP3i_fOW9yklwrvd3hQrb-qZKXoPDg9fIxjrU9LlKFwVGWobC56bAl7sGTBo3Lz1HOceZOEw_4Ck6XAjZr-eqTYvLdZS_nsV1S9zzY6RB9qda_e_Hs-l68go3946OhHB6MDp_DXdSaNUTBbVivpzPzAu7oeT2ppi-dzRL4drNI_wPqfXs-
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFD4aAzFeuGxcAgOMBLxA1DR2YvsBoaqjYtqoKoHQnhY5jqMVQTKatKz_jJ_HsZN0KhN72wPPcRzb-Y6PL9_5DsDLOEqVYH3hp1TkPsvizE_jUPh5bgKtBM7K1AUKH_LxWBwdyckG_O5iYSytspsT3USdldqekffQLdEYnXdMe3lLi5jsjd6f_vRtBil709ql02ggcmCWv3D7Vr3b38N__SoMRx--DD_6bYYBXzPOaj-kOpOxtiESOsdmZ6GMqLSq51GuqA6kYTyPMyzEDI0V2oNQgVFcyzQShmKt1-A6t5LljjQ46XwAttSdLFp9M5-xKGjDdQIqehW6TEtTCi2PiYXcP1t3iRfWuRfpmn_d2TpXOLrz_w7iXbjdLr_JoLGXe7Bhim3YGRSqLn8syWviCLHupmEbtoZdMrwd-GpVvKbFvJxXpFkFmIyYRWu3pMyJIo7Or2sy_DZUlSQLhbZd1MSedJN0VqqMTAafmlJ1w0le3ofPV9DXB7BZlIV5BERIrEJJrEIrFqtU9HMllZVe0jwNtfCg32Ei0a1au00a8j1xrAEqkgZHCeIocThKzjx4s3rntNEqubT0boeRpJ23quQcIB68WD3GsbbXSKowOMpJKKxmHdbEPXjYIHP1Oco5ruip9ICvYXZVwKqZrz8ppidO1ZzHdqvd9-Bth-7zZv27F48v78VzuIkATw73xwdP4BY2mjX8wV3YrGdz8xRu6EU9rWbPnPkSOL5aoP8BLMCD-w
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Continuous+directed+evolution+of+a+compact+CjCas9+variant+with+broad+PAM+compatibility&rft.jtitle=Nature+chemical+biology&rft.au=Schmidheini%2C+Lukas&rft.au=Mathis%2C+Nicolas&rft.au=Marquart%2C+Kim+Fabiano&rft.au=Rothgangl%2C+Tanja&rft.date=2024-03-01&rft.eissn=1552-4469&rft.volume=20&rft.issue=3&rft.spage=333&rft_id=info:doi/10.1038%2Fs41589-023-01427-x&rft_id=info%3Apmid%2F37735239&rft.externalDocID=37735239
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1552-4450&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1552-4450&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1552-4450&client=summon