Rational design and characterisation of an amphipathic cell penetrating peptide for non-viral gene delivery

Emma M. McErlean, Cian M. McCrudden, John W. McBride, Grace Cole, Vicky L. Kett, Tracy Robson, Nicholas J. Dunne, Helen O. McCarthy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
140 Downloads (Pure)


RALA is a cationic amphipathic peptide which has shown great promise as an efficient, multifunctional delivery system for the delivery of nucleic acids. Rational peptide design was utilised in this study to understand the essential amino acids required for delivery and if any improvements to the RALA peptide could be made. Six amphipathic peptides were synthesised with strategic sequences and amino acid substitutions to reduce peptide sequence, while maintaining the functional characteristics of RALA including amphipathicity, alpha-helicity and pH responsiveness for endosomal escape. Data demonstrated that all six peptides complexed pEGFP-N1 to produce cationic nanoparticles <200 nm in diameter, but not all peptides resulted in successful transfection; indicating the influence of peptide design for cellular uptake and endosomal escape. Pep2, produced nanoparticles with similar characteristics and transfection efficiency to the parent peptide, RALA. However, Pep2 had issues with toxicity and a lack of pH-responsive alpha-helcity. Therefore, RALA remains the superior sequence for non-toxic gene delivery.

Original languageEnglish
Article number120223
Number of pages13
JournalInternational Journal of Pharmaceutics
Early online date27 Jan 2021
Publication statusPublished - 01 Mar 2021

Bibliographical note

Funding Information:
Department for the Economy, Northern Ireland.

Publisher Copyright:
© 2021 Elsevier B.V.

Copyright 2021 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Pharmaceutical Science


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