# The Disruption of the HIV-1 Gag Start Codon via Editing Using MmCas12m-Dual Base Editor-Loaded Virus-like Particles

## TL;DR

Researchers used virus-like particles to deliver gene editing tools to disrupt the HIV-1 gag gene, showing potential for safer genomic editing.

## Contribution

The study demonstrates the use of virus-like particles for delivering ribonucleoprotein complexes to edit the HIV-1 genome with minimal genotoxicity.

## Key findings

- VLPs successfully delivered MmCas12m–TadDE to disrupt the HIV-1 gag gene start codon.
- VLPs showed minimal off-target effects and an editing efficiency of about 9%.
- VLPs lack nucleic acids, reducing the risk of insertional mutagenesis compared to traditional viral vectors.

## Abstract

Approaches to delivering gene editing tools in the form of ribonucleoproteins may provide a safety advantage over the delivery of nucleic acids encoding ribonucleoproteins. Virus-based vectors are widely used as a delivery platform. However, the persistence of viral exogenous nucleic acids can cause increased genotoxicity. Virus-like particles (VLPs) do not contain an expression cassette and can act as a platform for the delivery of ready-made ribonucleoprotein complexes. The absence of nucleic acids in VLPs eliminates the risk of insertional mutagenesis compared to widely used lentiviruses or adeno-associated viruses. Therefore, we used VLPs to deliver the ribonucleoprotein complex MmCas12m–TadDE to disrupt the HIV-1 gag gene start codon. We detected VLP morphogenesis using electron microscopy. We confirmed the incorporation of MmCas12m–TadDE into VLPs. We achieved an editing efficiency of about 9% in some cases with minimal off-target effects, which confirms the prospect of using VLPs as a platform for delivering genomic editing tools.