This review focuses on
antisense oligonucleotides and small interfering
ribonucleic acid therapies approved or under development for the management of
lipid disorders. Recent advances in
RNA-based
therapeutics allow tissue-specific targeting improving safety. Multiple potential target
proteins have been identified and
RNA-based
therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic
cardiovascular disease. The advantages of
RNA-based
lipid modifying
therapies include the ability to reduce the concentration of almost any target
protein highly selectively, allowing for more precise control of metabolic pathways than can often be achieved with small molecule-based drugs.
RNA-based
lipid modifying
therapies also make it possible to reduce the expression of target
proteins for which there are no small molecule inhibitors.
RNA-based
therapies can also reduce pill burden as their administration schedule typically varies from weekly to twice yearly
injections. The safety profile of most current
RNA-based
lipid therapies is acceptable but adverse events associated with various
therapies targeting
lipid pathways have included
injection site reactions, inflammatory reactions, hepatic steatosis and
thrombocytopenia. While the body of evidence for these
therapies is expanding, clinical experience with these
therapies is currently limited in duration and the results of long-term studies are eagerly awaited.