Reality check: lipid-oligonucleotide conjugates for therapeutic applications

Introduction Despite much progress in the field of oligonucleotide therapeutics, delivery in general remains an important aspect for innovation. Various lipids and lipophilic small molecules have long been conjugated to many oligonucleotides in hopes of creating better, drug-like substances. A few conjugates are beginning to enter clinical development as the understanding grows of how such conjugations change the pharmacology of the conjugate relative to the unmodified oligonucleotide. The delivery of different forms of oligonucleotides, such as antisense oligonucleotides and siRNA, is often a challenging, limiting aspect to this form of therapeutics.