New Approaches for Targeting PCSK9: Small-Interfering Ribonucleic Acid and Genome Editing.
Reindert F OostveenAmit V KheraSekar KathiresanErik S G StroesKevin FitzgeraldMatthew J HarmsBenjamin L OakesJohn J P KasteleinPublished in: Arteriosclerosis, thrombosis, and vascular biology (2023)
There is overwhelming clinical and genetic evidence supporting the concept that low-density-lipoprotein cholesterol should be as low as possible for as long as possible in patients at very high cardiovascular risk. Despite the wide availability of effective lipid-lowering therapies, the majority of patients still fail to reach guideline-based lipid goals. Advances in novel approaches targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) through small-interfering RNA and genome editing hold the potential to bridge this gap, by offering long-acting alternatives, which may overcome adherence and other challenges in the current chronic care model. In this review, we discuss the history of targeting PCSK9 with the use of mRNA and small-interfering ribonucleic acid. We also shed light on targeting PCSK9 with genome editing, including discussion of the VERVE-101 clustered regularly interspaced short palindromic repeats-base editing medicine currently being evaluated in a clinical trial and others in development.
Keyphrases
- genome editing
- crispr cas
- low density lipoprotein
- cancer therapy
- clinical trial
- end stage renal disease
- healthcare
- ejection fraction
- newly diagnosed
- drug delivery
- genome wide
- peritoneal dialysis
- metabolic syndrome
- public health
- gene expression
- prognostic factors
- health insurance
- affordable care act
- randomized controlled trial
- risk assessment
- climate change
- phase ii