In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector

RNA virus-based episomal vector (REVec) is an emerging viral vector system that mediates long-term stable gene expression in variety of cell types in vitro . However, little is known about its tissue tropism and persistence of gene expression in vivo . Here, to evaluate the feasibility of REVec for...

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Veröffentlicht in:	Scientific reports Jg. 10; H. 1; S. 5890 - 12
Hauptverfasser:	Komatsu, Yumiko, Tanaka, Chiaki, Komorizono, Ryo, Tomonaga, Keizo
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 03.04.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	631/1647/2300 631/326/596/2561 Animals Animals, Genetically Modified Antibodies, Neutralizing - blood Antibodies, Viral - blood Astrocytes Astrocytes - metabolism Body weight Brain - metabolism CD8 antigen Feasibility Studies Feces - virology Female Gene Expression Gene transfer Genetic Vectors - administration & dosage Genetic Vectors - genetics Genetic Vectors - isolation & purification Genetic Vectors - pharmacokinetics Humanities and Social Sciences Lymphocytes T Microglia Microglia - metabolism multidisciplinary Neurons - metabolism Pathogenicity Pathogens Plasmids - genetics Rats Rats, Inbred Lew RNA viruses RNA Viruses - genetics RNA Viruses - immunology RNA Viruses - isolation & purification Science Science (multidisciplinary) Tissue Distribution Transduction, Genetic Transgenes - genetics Tropism Virus Replication Virus Shedding
ISSN:	2045-2322, 2045-2322
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Zusammenfassung:	RNA virus-based episomal vector (REVec) is an emerging viral vector system that mediates long-term stable gene expression in variety of cell types in vitro . However, little is known about its tissue tropism and persistence of gene expression in vivo . Here, to evaluate the feasibility of REVec for in vivo gene delivery, we conducted biodistribution analysis of transmission competent REVec and transmission defective ΔG-REVec in Lewis rats. Following intracranial administration of REVec, transgene expression was detected in various tissues. In contrast, transgene expression was only observed in the brain after ΔG-REVec administration. Low levels of vector shedding in the feces and blood and of neutralizing antibody in the serum were detected after REVec injection. In the brain, microglia, astrocytes and neurons were susceptible to REVec-mediated transduction. However, the animals administered with REVec, but not with ΔG-REVec showed a significant decrease in body weight compared to mock treated animals. Additionally, CD8 T cell infiltration was observed in the brain of these animals. In summary, we demonstrated that REVec promotes long-term transgene expression in vivo without causing high vector shedding or neutralizing antibody production; however, suggests the need to attenuate vector associated pathogenicity in the future.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-62630-7