TY  - JOUR
N2  - 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 in vitro and in vivo. This has a potential application in gene and cell therapy scenarios requiring temporary payload expression in cells and tissues that can be targeted with pseudotyped LV vectors.
VL  - 20
AV  - public
N1  - © 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
TI  - Re-structuring lentiviral vectors to express genomic RNA via cap-dependent translation
SP  - 357
EP  - 365
ID  - discovery10121414
JF  - Molecular Therapy - Methods and Clinical Development
Y1  - 2021/03/12/
A1  - Counsell, JR
A1  - De Brabandere, G
A1  - Karda, R
A1  - Moore, M
A1  - Greco, A
A1  - Bray, A
A1  - Diaz, JA
A1  - Perocheau, DP
A1  - Mock, U
A1  - Waddington, SN
UR  - https://doi.org/10.1016/j.omtm.2020.12.005
ER  -