Therapeutic oligonucleotides in cardiovascular and metabolic diseases: insights for the internist

Internal and Emergency Medicine
Domenico GirelliOliviero Olivieri

Abstract

The idea of using small RNA fragments (oligonucleotides) for therapeutic purposes dates back to the 1990s, following the landmark discoveries on the mechanisms of gene silencing and RNA-interference (RNA-i). However, the first applications in medicine were hampered by difficulties in chemical stabilization and efficient delivery to target tissues. Recent advances in chemical manipulation of oligonucleotides have, at least partially, bypassed such obstacles. In particular, conjugation with ligands for specific receptors allows the selective uptake of oligonucleotides by critical cells (e.g., hepatocytes), where they inhibit the synthesis of the target protein by binding the complementary mRNA and inducing its degradation. In parallel, next-generation sequencing (NGS) studies at population levels have identified a number of key molecular targets, mainly through the discovery of "human knock-outs," i.e., subjects lacking a given protein because of nonsense mutations in the corresponding gene. Such highly informative individuals are often healthy, or even protected from the development of certain diseases. Indeed, subjects with null mutations in certain genes controlling lipoprotein metabolism like PCSK9 or ANGPTL-3 have a lower ri...Continue Reading

References

Dec 17, 2009·Seminars in Thrombosis and Hemostasis·Domenico GirelliOliviero Olivieri
May 17, 2014·Science·Jocelyn Kaiser
Oct 18, 2014·Nature Reviews. Drug Discovery·Adrienne D CoxChanning J Der
Dec 2, 2014·Journal of the American Chemical Society·Jayaprakash K NairMuthiah Manoharan
Dec 9, 2014·The New England Journal of Medicine·Harry R BüllerUNKNOWN FXI-ASO TKA Investigators
Mar 19, 2015·The New England Journal of Medicine·Giovanni MonteleoneFrancesco Pallone
Jul 30, 2015·The New England Journal of Medicine·Daniel GaudetJohn J P Kastelein
May 21, 2016·Cell·Pradeep Natarajan, Sekar Kathiresan
Oct 1, 2016·Trends in Cardiovascular Medicine·Nathan O Stitziel, Sekar Kathiresan
Oct 13, 2016·Annual Review of Pharmacology and Toxicology·C Frank BennettRichard S Geary
Dec 14, 2016·The New England Journal of Medicine·Kevin FitzgeraldAmy Simon
Jan 5, 2017·The New England Journal of Medicine·Anastasia Khvorova
Feb 12, 2017·Journal of the American College of Cardiology·Sotirios Tsimikas
Mar 1, 2017·Nature Biotechnology·Anastasia Khvorova, Jonathan K Watts
Mar 14, 2017·Nature Reviews. Genetics·Amit V Khera, Sekar Kathiresan
Mar 18, 2017·The New England Journal of Medicine·Kausik K RayJohn J P Kastelein
Apr 8, 2017·Journal of the American College of Cardiology·Nathan O StitzielUNKNOWN PROMIS and Myocardial Infarction Genetics Consortium Investigators
Apr 12, 2017·European Journal of Internal Medicine·Domenico GirelliOliviero Olivieri
Apr 12, 2017·JAMA : the Journal of the American Medical Association·Stanley F Nelson, M Carrie Miceli
Apr 12, 2014·Nature·Robert M Plenge
Jul 7, 2017·Nature Reviews. Cardiology·Dario Ummarino
Nov 5, 2017·Cold Spring Harbor Perspectives in Medicine·Matthew Holderfield
Nov 15, 2017·Neuromuscular Disorders : NMD·Sonia MessinaUNKNOWN Italian EAP working Group
Dec 6, 2017·Neuromuscular Disorders : NMD·Nathalie GoemansUNKNOWN DEMAND III study group

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Citations

Jun 22, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yi-Zhang LiuLiang Huang
Jan 5, 2019·Bioconjugate Chemistry·Sebastien BenizriPhilippe Barthélémy

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