Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.

Oligonucleotides have been identified as powerful therapeutics for treating genetic disorders and diseases related to epigenetic factors such as metabolic and immunological dysfunctions. However, they face certain obstacles in terms of limited delivery to tissues and poor cellular uptake due to their large size and often highly charged nature. Peptide-oligonucleotide conjugation is an extensively utilized approach for addressing the challenges associated with oligonucleotide-based therapeutics by improving their delivery, cellular uptake and bioavailability, consequently enhancing their overall therapeutic efficiency.

Thiol-Specific Linkers for the Synthesis of Oligonucleotide Conjugates via Metal-Free Thiol-Ene Click Reaction.

Chemical conjugation of oligonucleotides is widely used to improve their delivery and therapeutic potential. A variety of strategies are implemented to efficiently modify oligonucleotides with conjugating partners. The linkers typically used for oligonucleotide conjugation have limitations in terms of stability or ease of synthesis, which generates the need for providing new improved linkers for oligonucleotide conjugation.