Gene Delivery in Lipid Research and Therapies

Methodist Debakey Cardiovasc J. Jan-Mar 2019;15(1):62-69. doi: 10.14797/mdcj-15-1-62.

Abstract

Cardiovascular disease is the leading cause of death worldwide, and elevated lipid levels is a major contributor. Gene delivery, which involves controlled transfer of nucleic acids into cells and tissues, has been widely used in research to study lipid metabolism and physiology. Several technologies have been developed to somatically overexpress, silence, or disrupt genes in animal models and have greatly advanced our knowledge of metabolism. This is particularly true with regard to the liver, which plays a central role in lipoprotein metabolism and is amenable to many delivery approaches. In addition to basic science applications, many of these delivery technologies have potential as gene therapies for both common and rare lipid disorders. This review discusses three major gene delivery technologies used in lipid research-including adeno-associated viral vector overexpression, antisense oligonucleotides and small interfering RNAs, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing system-and examines their potential therapeutic applications.

Keywords: CRISPR/Cas9; Clustered Regularly Interspaced Short Palindromic Repeats; adeno-associated viral vector; antisense oligonucleotides; gene therapy; genome editing; lipoprotein metabolism; small interfering RNAs.

Publication types

  • Review

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / prevention & control*
  • Dependovirus / genetics
  • Dyslipidemias / blood
  • Dyslipidemias / epidemiology
  • Dyslipidemias / genetics
  • Dyslipidemias / therapy*
  • Gene Editing / methods
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Lipid Metabolism / genetics*
  • Lipids / blood*
  • Oligonucleotides, Antisense / genetics
  • RNA, Small Interfering / genetics
  • RNAi Therapeutics / methods
  • Treatment Outcome

Substances

  • Lipids
  • Oligonucleotides, Antisense
  • RNA, Small Interfering