title: Gene-based therapies in lipidology: current status and future challenges.
abstract: OBJECTIVE
  Gene-based therapies are designed to modulate gene expression in specific tissues by introducing into cells transgenes, antisense oligonucleotides, RNA interference, microRNAs, or a variety of other oligonucleotide-based compounds and their delivery systems. Several types of gene-based therapies are already available or in clinical development to treat severe lipid-related disorders and associated risk. The review briefly presents the current status and future challenges of these therapies in clinical lipidology, focusing on most advanced and promising agents or mechanisms.
  
  
  RESULTS
  Gene-based agents address several unmet medical needs in lipidology such as homozygous familial hypercholesterolemia, familial or multifactorial chylomicronemia, severe hypertriglyceridemia, elevated lipoprotein (a), familial partial lipodystrophy, nonalcoholic fatty liver disease, and hypoalphalipoproteinemia. Most advanced antisense oligonucleotide drugs target apolipoprotein C-III, apolipoprotein (a), angiopoietin-like 3, and diacylglycerol o-acyltransferase-2. Long-term efficacy and safety data are now available for two gene-based agents, mipomersen, approved in the USA for homozygous familial hypercholesterolemia and Glybera, AAV1-LPLS447X gene therapy, conditionally approved in Europe for lipoprotein lipase deficiency.
  
  
  CONCLUSIONS
  Although positive to date, the overall benefit-risk ratio of gene-based therapies is yet to be documented long term across additional patients and conditions. The next generation of such therapies might improve their therapeutic index.
authors.affiliation: Lipidology Unit, Community genomic medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21, Chicoutimi, Quebec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
mesh_terms: D000818:Animals; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D023281:Genomics; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering