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Biosafety features of lentiviral vectors
- Source :
- Human gene therapy. 24(2)
- Publication Year :
- 2013
-
Abstract
- Over the past decades, lentiviral vectors have evolved as a benchmark tool for stable gene transfer into cells with a high replicative potential. Their relatively flexible genome and ability to transduce many forms of nondividing cells, combined with the potential for cell-specific pseudotyping, provides a rich resource for numerous applications in experimental platforms and therapeutic settings. Here, we give an overview of important biosafety features of lentiviral vectors, with detailed discussion of (i) the principles of the lentiviral split-genome design used for the construction of packaging cells; (ii) the relevance of modifications introduced into the lentiviral long terminal repeat (deletion of enhancer/promoter sequences and introduction of insulators); (iii) the basic features of mRNA processing, including the Rev/Rev-responsive element (RRE) interaction and the modifications of the 3′ untranslated region of lentiviral vectors with various post-transcriptional regulatory elements affecting transcriptional termination, polyadenylation, and differentiation-specific degradation of mRNA; and (iv) the characteristic integration pattern with the associated risk of transcriptional interference with cellular genes. We conclude with considerations regarding the importance of cell targeting via envelope modifications. Along this course, we address canonical biosafety issues encountered with any type of viral vector: the risks of shedding, mobilization, germline transmission, immunogenicity, and insertional mutagenesis.
- Subjects :
- Untranslated region
Virus Integration
Genetic Vectors
Mutagenesis (molecular biology technique)
Reviews
Computational biology
Genome, Viral
Biology
Virus Replication
Genome
Biosafety
Genetics
Humans
RNA Processing, Post-Transcriptional
Enhancer
Promoter Regions, Genetic
Molecular Biology
Lentivirus
Gene Transfer Techniques
Long terminal repeat
Virus Shedding
Mutagenesis, Insertional
Enhancer Elements, Genetic
Pseudotyping
Lentivirus Infections
Molecular Medicine
Virus Activation
Subjects
Details
- ISSN :
- 15577422
- Volume :
- 24
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Human gene therapy
- Accession number :
- edsair.doi.dedup.....4ccbd04ae686cfbf25441eae39f10370