Re-structuring lentiviral vectors to express genomic RNA via cap-dependent translation.
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
12 Mar 2021
12 Mar 2021
Historique:
received:
06
03
2020
accepted:
01
12
2020
entrez:
8
2
2021
pubmed:
9
2
2021
medline:
9
2
2021
Statut:
epublish
Résumé
Lentiviral (LV) vectors based on human immunodeficiency virus type I (HIV-1) package two copies of their single-stranded RNA into vector particles. Normally, this RNA genome is reverse transcribed into a double-stranded DNA provirus that integrates into the cell genome, providing permanent gene transfer and long-term expression. Integration-deficient LV vectors have been developed to reduce the frequency of genomic integration and thereby limit their persistence in dividing cells. Here, we describe optimization of a reverse-transcriptase-deficient LV vector, which enables direct translation of LV RNA genomes upon cell entry, for transient expression of vector payloads as mRNA without a DNA intermediate. We have engineered a novel LV genome arrangement in which HIV-1 sequences are removed from the 5' end, to enable ribosomal entry from the 5' 7-methylguanylate cap for efficient translation of the vector payload. We have shown that this LV-mediated mRNA delivery platform provides transient transgene expression
Identifiants
pubmed: 33553484
doi: 10.1016/j.omtm.2020.12.005
pii: S2329-0501(20)30253-9
pmc: PMC7838728
doi:
Types de publication
Journal Article
Langues
eng
Pagination
357-365Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210774/Z/18/Z
Pays : United Kingdom
Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
J.R.C. and G.D.B. are inventors on a patent application covering the technology described in this manuscript. The other authors declare no competing interests.
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