Improved method for synthesis of low molecular weight protamine-siRNA conjugate

A monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA were developed via a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Three different synthetic and purification methods were compared and hetero-bifunctional NHS-PEG-OPSS was the optimized crosslinker.167