The chemistry and biology of oligonucleotide conjugation

A major challenge associated with oligonucleotide nucleic acid therapeutics is the difficulty of these relatively large and often highly charged molecules to cross cellular membranes and reach their sites of action in the cytosol or nucleus. Consequently, unfavorable pharmacokinetic or pharmacodynamic properties and inefficient cellular uptake currently limit their full translational potential. In order to address these important issues, chemical conjugation of oligonucleotides with molecular transporters is used to improve nucleic acid therapeutic delivery and therefore enhance the clinical efficacy of these compounds.

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