RfxCas13d-loaded VLP

RfxCas13d-loaded VLP is a CRISPR-based RNA editing therapeutic candidate designed for the targeted knockdown of PCSK9 mRNA. Developed by researchers at the University at Buffalo, the system utilizes virus-like nanoparticles (VLPs) to deliver Ruminococcus flavefaciens Cas13d (RfxCas13d) as a ribonucleoprotein (RNP) complex. Unlike traditional CRISPR-Cas9 systems that target DNA, RfxCas13d specifically binds and cleaves RNA, offering a transient and potentially safer method for gene silencing without the risk of permanent genomic alterations. In the context of hypercholesterolemia, the VLP-mediated delivery of RfxCas13d RNPs to the liver results in the degradation of PCSK9 transcripts, which in turn increases the expression of low-density lipoprotein (LDL) receptors and facilitates the clearance of LDL cholesterol from the bloodstream. Preclinical studies have demonstrated that this approach can achieve significant reductions in PCSK9 mRNA and protein levels, showing superior efficacy compared to existing siRNA-based therapies like inclisiran.