Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery

The design of a non-viral gene delivery system that can release functional nucleic acid at the intracellular destination site is an exciting but also challenging proposition. ideal vector must be non-toxic, non-immunogenic, overcome extra- and intra-cellular barriers, protect cargo from degradation with stability over range temperatures. A new 15 amino linear peptide termed CHAT was designed in this study goal delivering DNA high efficiency into cells vitro tissues vivo. Rational involved incorporation key acids including arginine for complexation cellular uptake, tryptophan to enhance hydrophobic interaction cell membranes, histidine facilitate endosomal escape cysteine controlled release. Six peptides were synthesised strategic sequences substitutions. Data demonstrated all six complexed pDNA produce cationic nanoparticles less than 200 nm diameter, not resulted successful transfection; indicating influence escape. Peptide 4, now CHAT, non-cytotoxic, traversed plasma membrane breast prostate cancer lines, elicited reporter-gene expression following intra-tumoural intravenous presents therapeutics.