Messenger RNA

Cell

Translation (biology)

Nanotechnology

Organic chemistry

Covalent bond

Cell-penetrating peptide

Biology

Gene

Oligonucleotide

Bioavailability

Chemistry

Materials science

Nucleic acid

Computational biology

Biochemistry

Pharmacology

Biomedicines

The promise of nucleic acid based oligonucleotides as effective genetic therapies has been held back by their low bioavailability and poor cellular uptake to target tissues upon systemic administration. One such strategy to improve upon delivery is the use of short cell-penetrating peptides (CPPs) that can be either directly attached to their cargo through covalent linkages or through the formation of noncovalent nanoparticle complexes that can facilitate cellular uptake. In this review, we will highlight recent proof-of-principle studies that have utilized both of these strategies to improve nucleic acid delivery and discuss the prospects for translation of this approach for clinical application.

Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics