Anti-HIV-1 potency of the CRISPR/Cas9 system insufficient to fully inhibit viral replication.
The range of genome-editing tools has recently been expanded. In particular, an RNA-guided genome-editing tool, the clustered regularly interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, has many applications for human diseases. In this study, guide RNA (gRNA) to target gag, pol and a long terminal repeat of HIV-1 was designed and used to generate gRNA-expressing lentiviral vectors. An HIV-1-specific gRNA and Cas9 were stably dually transduced into a highly HIV-1-susceptible human T-cell line and the inhibitory ability of the anti-HIV-1 CRISPR/Cas9 lentiviral vector assessed. Although clear inhibition of the early phase of HIV-1 infection was observed, as evaluated by a VSV-G-pseudotyped HIV-1 reporter system, the anti-HIV-1 potency in multiple rounds of wild type (WT) viral replication was insufficient, either because of generation of resistant viruses or overcoming of the activity of the WT virus. Thus, there are potential difficulties that must be addressed when considering anti-HIV-1 treatment with the CRISPR/Cas9 system alone.
['Ueda|Shuhei|S|', 'Ebina|Hirotaka|H|', 'Kanemura|Yuka|Y|', 'Misawa|Naoko|N|', 'Koyanagi|Yoshio|Y|']
D064113:CRISPR-Cas Systems D002460:Cell Line D002478:Cells, Cultured D000072669:Gene Editing D018390:Gene Targeting D005814:Genes, Viral D015658:HIV Infections D015497:HIV-1 D006801:Humans D009154:Mutation D017394:RNA, Guide D016662:Virus Integration D014779:Virus Replication
anti-HIV-1 potency CRISPR T cell