TY - JOUR

T1 - The Disruption of the HIV-1 Gag Start Codon via Editing Using MmCas12m-Dual Base Editor-Loaded Virus-like Particles

AU - Aliev, Timur

AU - Imatdinov, Almaz

AU - Prudnikova, Elena

AU - Taranov, Oleg

AU - Emtsova, Ksenia

AU - Imatdinov, Ilnaz

AU - Agafonov, Alexander

N1 - The Disruption of the HIV-1 Gag Start Codon via Editing Using MmCas12m-Dual Base Editor-Loaded Virus-like Particles / T. Aliev, A. Imatdinov, E. Prudnikova [et al.] // Current Issues in Molecular Biology. – 2026. – Vol. 48, No. 3. – P. 241. – DOI 10.3390/cimb48030241. – EDN ODNMJT. This research was funded by the Ministry of Science and Higher Education of the Russian Federation (The Federal Scientific-technical programme for genetic technologies development for 2019–2030, agreement No. 075-15-2025-526).

PY - 2026/2/25

Y1 - 2026/2/25

N2 - 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.

AB - 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.

KW - CRISPR/Cas

KW - HIV

KW - MmCas12m

KW - base editing

KW - gene therapy

KW - virus-like particles

KW - ВИЧ

KW - генная терапия

KW - редактирование оснований

KW - CRISPR/Cas

KW - MmCas12m

KW - вирусоподобные частицы

UR - https://www.mendeley.com/catalogue/f907f14c-6fef-36e3-9eba-c0008f3fab2b/

UR - https://www.scopus.com/pages/publications/105033710250

UR - https://elibrary.ru/item.asp?id=89957759

U2 - 10.3390/cimb48030241

DO - 10.3390/cimb48030241

M3 - Article

C2 - 41899394

VL - 48

JO - Current issues in molecular biology

JF - Current issues in molecular biology

SN - 1467-3037

IS - 3

M1 - 241

ER -