CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1.
C46 HIV-1 fusion inhibitor
CCR5 CRISPR/Cas9
HIV-1 gene therapy
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 05 2024
13 05 2024
Historique:
received:
20
10
2023
accepted:
07
05
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
Hematopoietic stem-cell (HSC) transplantation using a donor with a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as a cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from HIV infection by this approach. However, finding a naturally suitable Human Leukocyte Antigen (HLA)-matched homozygous CCR5Δ32 donor is very difficult. The prevalence of this allele is only 1% in the Caucasian population. Therefore, additional sources of CCR5Δ32/Δ32 HSCs are required. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system is one method to mediate CCR5 knockout in HSCs that has been successfully employed as a gene editing tool in clinical trials. Additional anti-HIV-1 strategies are still required for broad-spectrum inhibition of HIV-1 replication. Here in this study, we combined an additional anti-HIV-1 therapy, which is C46, a cell membrane-anchored HIV-1 fusion inhibitor with the CRISPR/Cas9 mediated knockout CCR5. The combined HIV-1 therapeutic genes were investigated for the potential prevention of both CCR5 (R5)- and CXCR4 (X4)-tropic HIV-1 infections in the MT4CCR5 cell line. The combinatorial CRISPR/Cas9 therapies were superior compared to single method therapy for achieving the HIV-1 cure strategy and shows potential for future applications.
Identifiants
pubmed: 38741006
doi: 10.1038/s41598-024-61626-x
pii: 10.1038/s41598-024-61626-x
doi:
Substances chimiques
Receptors, CCR5
0
CCR5 protein, human
0
HIV Fusion Inhibitors
0
C46 HIV-1 fusion inhibitory peptide
0
Recombinant Fusion Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10852Subventions
Organisme : Office of National Higher Education Science Research and Innovation Policy Council through the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (PMU-B)
ID : B05F630063
Organisme : King Mongkut's Institute of Technology Ladkrabang
ID : 2563-0216006
Informations de copyright
© 2024. The Author(s).
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