Folding-Mediated DNA Delivery by α‑Helical Amphipathic Peptides

• Published in: ACS biomaterials science & engineering Vol. 9; no. 5; pp. 2584 - 2595
• Main Authors: Noble, James E., Vila-Gómez, Paula, Rey, Stephanie, Dondi, Camilla, Briones, Andrea, Aggarwal, Purnank, Hoose, Alex, Baran, Maryana, Ryadnov, Maxim G.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08-05-2023
• Subjects: Amino Acid Sequence; Controlled Release and Delivery Systems; DNA - chemistry; DNA - genetics; DNA - metabolism; Genetic Therapy; Humans; Peptides - chemistry; Transfection; transfection reagents; α-helix; gene therapy; nonviral vectors; cell-penetrating peptides
• ISSN: 2373-9878; 2373-9878
• DOI: 10.1021/acsbiomaterials.3c00221

The renaissance gene therapy experiences these days requires specialist biomaterials and a systemic understanding of major factors influencing their ability to deliver genetic material. Peptide transfection systems represent a major class of such biomaterials. Several peptidic reagents have been commercialized to date. However, a comparative assessment of peptide sequences alone without auxiliary support or excipients against a common determinant for their ability to complex and deliver DNA has been lacking. This study cross-compares commercial and experimental transfection reagents from the same family of helical amphiphiles. Factors defining the efficacy of DNA delivery including cell uptake and gene expression are assessed along with cytotoxicity and DNA complexation. The results show that despite differences in sequence composition, length, and origin, peptide reagents of the same structural family exhibit similar characteristics and limitations with common variability trends. The cross-comparison revealed that functional DNA delivery is independent of the peptide sequence used but is mediated by the ability of the reagents to co-fold with DNA. Peptide folding proved to be the common determinant for DNA complexation and delivery by peptidic transfection reagents.