Using combined synthetic gene-editing tools to block HIV replication and gene activity

Sequential or combinatorial treatments with gRNA4/Cas9 and/or gRNA5/Cas12a RNPs resulted in significant reductions in integrated proviral DNA and HIV mRNA levels.

• Synthetic gRNA/Cas12a and gRNA/Cas9 ribonucleoproteins demonstrated specificity and efficacy in disrupting HIV gene replication.
• Treatment with gRNA4/Cas9 and gRNA5/Cas12a RNPs led to a notable decrease in p24 protein levels.
• High rates of insertion and deletion or knockout frequencies were observed at HIV target genes.
• Gene alignment analysis indicated a high level of conservation in target sequences across diverse regional HIV strains.
• These findings suggest potential for targeting different HIV strains globally.

Simplified