Executive Summary : | Gene therapy is a promising method for treating genetic diseases through gene silencing or expression. However, the cell membrane's penetrability to nucleic acids remains a significant obstacle in the development of gene and antisense therapy. Over the past decade, various cationic polymers, cell-penetrating peptides, nanoparticles, and liposomes have been designed as vectors to transfect mammalian cells. Peptides have gained interest due to their biochemical and biophysical stability, simplicity, and ease of synthesis. However, few peptide-based carriers have been reported for oligonucleotide delivery, and their clinical application is not yet successful. A tryptophan, arginine, and cysteine-based cyclic peptide has been reported as an efficient nucleic acid delivery system, but the synthesis process is time-consuming and yields are less than linear peptides. To address this issue, a library of peptide sequences can be developed to optimize the delivery of therapeutic oligonucleotides. Different hydrophobic and hydrophilic sequences need to be designed and their self-assembled nanostructures investigated. To develop a combination cancer drug delivery system, different anti-cancer oligonucleotides such as VEGF, PDGFR, c-Myc, p53, BRCA1, BRAC 2, ras, and RAF will be investigated for delivery. The proposed sequences include Ac-RRRGGGCWWWWCGGGRRR-NH2 (W4C2R6), Ac-RRRRGGGCWWWWCGGGRRR-NH2 (W2C2R6), and Ac-RRRRGGGCWWCGGGRRR-NH2 (W2C2R8). |