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

Timur Aliev1,2, Almaz Imatdinov1, Elena Prudnikova1

  • 1State Research Center of Virology and Biotechnology "Vector", 630559 Kol'tsovo, Russia.

Current Issues in Molecular Biology
|March 28, 2026
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Summary

Virus-like particles (VLPs) offer a safer gene editing delivery method by encapsulating ready-made ribonucleoprotein complexes. This approach avoids viral nucleic acid risks, minimizing genotoxicity and insertional mutagenesis for effective HIV-1 gene disruption.

Keywords:
CRISPR/CasHIVMmCas12mbase editinggene therapyvirus-like particles

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Area of Science:

  • Molecular Biology
  • Gene Editing Technologies
  • Virology

Background:

  • Ribonucleoprotein (RNP) delivery offers safety advantages over nucleic acid delivery for gene editing.
  • Virus-based vectors are common but pose genotoxicity risks due to persistent viral DNA.
  • Virus-like particles (VLPs) can package pre-formed RNPs, avoiding nucleic acid integration and associated risks.

Purpose of the Study:

  • To evaluate Virus-like Particles (VLPs) as a safe delivery platform for gene editing tools.
  • To assess the efficacy of VLP-delivered MmCas12m-TadDE ribonucleoprotein complex for HIV-1 gene disruption.

Main Methods:

  • Virus-like particles (VLPs) were engineered to encapsulate the MmCas12m-TadDE ribonucleoprotein complex.
  • VLP morphogenesis and RNP incorporation were confirmed using electron microscopy.
  • The VLP-RNP system was used to target and disrupt the HIV-1 gag gene start codon.

Main Results:

  • VLP formation and successful packaging of the MmCas12m-TadDE complex were confirmed.
  • Gene editing achieved approximately 9% efficiency in targeted disruption of the HIV-1 gag gene start codon.
  • Minimal off-target editing effects were observed, indicating a high degree of specificity.

Conclusions:

  • Virus-like particles (VLPs) represent a promising, safe, and effective platform for delivering gene editing ribonucleoprotein complexes.
  • VLP-mediated delivery mitigates risks associated with viral vectors, such as genotoxicity and insertional mutagenesis.
  • This VLP-based strategy holds potential for therapeutic gene editing applications, including targeting viral genes.