Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review

Cardiovasc Drugs Ther. 2023 Jun;37(3):585-598. doi: 10.1007/s10557-021-07293-w. Epub 2022 Jan 13.

Abstract

In recent years, the increase in available genetic information and a better understanding of the genetic bases of dyslipidemias has led to the identification of potential new avenues for therapies. Additionally, the development of new technologies has presented the key for developing novel therapeutic strategies targeting not only proteins (e.g., the monoclonal antibodies and vaccines) but also the transcripts (from antisense oligonucleotides (ASOs) to small interfering RNAs) or the genomic sequence (gene therapies). These pharmacological advances have led to successful therapeutic improvements, particularly in the cardiovascular arena because we are now able to treat rare, genetically driven, and previously untreatable conditions (e.g, familial hypertriglyceridemia or hyperchylomicronemia). In this review, the pre-clinical pharmacological development of the major biotechnological cholesterol lowering advances were discussed, describing facts, gaps, potential future steps forward, and therapeutic opportunities.

Keywords: Angptl3; Car-T therapy; LDLR; Lp(a); PCSK9; mAb.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal* / adverse effects
  • Anticholesteremic Agents* / adverse effects
  • Cholesterol
  • Cholesterol, LDL
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use
  • Proprotein Convertase 9 / genetics

Substances

  • Antibodies, Monoclonal
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Oligonucleotides, Antisense
  • Cholesterol
  • Proprotein Convertase 9