RALA peptide

RALA peptide is a 30-amino acid cationic, amphipathic cell-penetrating peptide (CPP) designed for non-viral gene and drug delivery. Originally developed as a spin-out from Queen's University Belfast and further advanced by pHion Therapeutics, RALA's sequence (N-WEARLARALARALARHLARALARALRACEA-C) is rich in arginine, alanine, leucine, and alanine. It self-assembles into stable nanoparticles (<200 nm) through electrostatic interactions with negatively charged cargo, such as plasmid DNA, mRNA, siRNA, miRNA, CRISPR machinery, and small anionic molecules (e.g., bisphosphonates). RALA exhibits pH-responsive conformational changes, transitioning to an alpha-helical structure in the acidic environment of the endosome (pH < 6), which facilitates endosomal membrane disruption and efficient cytosolic release of its cargo with minimal cytotoxicity. Although pHion Therapeutics entered administration in late 2024, RALA remains a widely studied delivery platform for therapeutic vaccines (such as PTX_V1 for HPV-related cancers) and gene therapies.

Other names

arginine-alanine-leucine-alanine peptideRALA