Academic Journal
Re-structuring lentiviral vectors to express genomic RNA via cap-dependent translation
| Title: | Re-structuring lentiviral vectors to express genomic RNA via cap-dependent translation |
|---|---|
| Authors: | John R. Counsell, Guillaume De Brabandere, Rajvinder Karda, Marc Moore, Antonio Greco, Alysha Bray, Juan Antinao Diaz, Dany P. Perocheau, Ulrike Mock, Simon N. Waddington |
| Source: | Molecular Therapy: Methods & Clinical Development, Vol 20, Iss , Pp 357-365 (2021) |
| Publisher Information: | Elsevier, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Genetics LCC:Cytology |
| Subject Terms: | Genetics, QH426-470, Cytology, QH573-671 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050120302539; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2020.12.005 |
| Access URL: | https://doaj.org/article/91dfe80765324ae6b172bc6c3bfd05e5 |
| Accession Number: | edsdoj.91dfe80765324ae6b172bc6c3bfd05e5 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23290501 |
|---|---|
| DOI: | 10.1016/j.omtm.2020.12.005 |
| Published in: | Molecular Therapy: Methods & Clinical Development |
| Language: | English |