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

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