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.
Institute for Virus Research.|Graduate School of Biostudies, Kyoto University, Kyoto 6068507, Japan.
Shuhei
S
Ueda
Institute for Virus Research.
Hirotaka
H
Ebina
Institute for Virus Research.
Yuka
Y
Kanemura
Institute for Virus Research.
Naoko
N
Misawa
Institute for Virus Research.
Yoshio
Y
Koyanagi
D064113:CRISPR-Cas Systems; D002460:Cell Line; D002478:Cells, Cultured; D000072669:Gene Editing; D018390:Gene Targeting; D005814:Genes, Viral; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D000094704:RNA, Guide, CRISPR-Cas Systems; D016662:Virus Integration; D014779:Virus Replication
D000094704:RNA, Guide, CRISPR-Cas Systems
CRISPR; T cell; anti-HIV-1 potency