title: Is there a future for cell-penetrating peptides in oligonucleotide delivery?
abstract: Cell-penetrating peptides have been widely investigated as delivery vehicles for oligonucleotides (e.g., siRNA and antisense oligonucleotides). Different delivery strategies can be used, such as co-incubation, direct conjugation, non-covalent complex, and modification on the surface of liposome or polymer complexes. However, several challenges remain for their preclinical and clinical development. Endosomal escape, lack of cell/tissue specificity, and toxicity are major concerns in the design of cell-penetrating peptide-mediated delivery systems. In this commentary, we highlight recent reports of cell-penetrating peptide incorporation into oligonucleotide delivery systems and underline the remaining challenges, particularly for preclinical and clinical applications.
authors: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zurich, Switzerland.
authors: Soo Hyeon
authors: SH
authors: Lee
authors: Bastien
authors: B
authors: Castagner
authors: Jean-Christophe
authors: JC
authors: Leroux
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000639:trends; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing; D015316:Genetic Therapy / Q000009:adverse effects / Q000639:trends; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering
keywords: Cell-penetrating peptide; Delivery; Endocytosis; Oligonucleotide; siRNA