Recently, small interfering RNA (siRNA), one kind of RNA interference (RNAi) technology represent the most common and, to date, the most effective method to inhibit target gene expression in human cells. It is also a common recognition that non-toxic delivery of siRNA is an urgent problem for the therapeutic application of siRNA. For the efficient gene silencing in vivo, prolonged circulation of siRNA with take efficient and non-toxic cellular uptake and resistance against enzymatic degradation are indispensably required.
Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics.
In the present study, we investigated the intracellular delivery using some hybrid peptides as transfection reagents and the silencing effect of siRNA targeting hTERT mRNA in 3 human cancer cell lines, Jurkat, HeLa and K562. The complex of siRNA and a specific amphiphilic peptide or its hybrid with an intracellular transport signal peptide could be effectively taken up into cells. The complex also showed a high silencing effect against hTERT mRNA. Moreover, the combination of siRNA-NES conjugates and the amphiphilic peptides improved silencing effects up to 95.2 %. The amphiphilic peptides and their hybrids showed almost no cyto-toxicity and protected siRNA against intracellular nuclease digestion in 10% FBS (half life time was over 48h).
Fujii M et al. (2017) Nucleic Acid Therapeutics 27(3):168-175.
Fujii M et al. (2020) Nucleosides, Nucleotides and Nucleic Acids 39(1-3):407-425.