LV-VLP-MA

LV-VLP-MA is an optimized lentivirus-derived virus-like particle (VLP) platform designed for the efficient in vivo delivery of genome editing tools, including Cas9 ribonucleoproteins (RNPs), base editors (BE), and prime editors (PE). Developed by researchers at Boston Children's Hospital and Dana-Farber Cancer Institute, the platform utilizes a specific configuration where the editor protein (e.g., Cas9) is fused to the matrix (MA) domain of the Gag polyprotein. This engineering maximizes the incorporation of large editor proteins into the particles without compromising functional titer. The particles are typically pseudotyped with VSVg to enable broad tropism. In preclinical studies, LV-VLP-MA has demonstrated high editing efficiency in primary human CD34+ cells, achieving indel frequencies up to 90%, and successful liver-restricted editing of the Pcsk9 locus in mice following systemic intravenous administration, leading to significant reductions in serum PCSK9 levels without detectable tissue pathology.