Effects of chirality on gene delivery efficiency of polylysine

Chirality is a key factor in the biological activity of many biomolecules. Poly(L-lysine) (PLL), a polypeptide synthesized from L-lysine, is one of the mostly used cationic polymers for gene delivery. The effect of chirality of polylysine (PL) on its gene delivery remains unknown. Herein, we prepared three polylysines (PLs) with the similar molecular weight but different backbone chiralities including poly(L-lysine) (PLL), poly(D-lysine) (PDL) and poly(DL-lysine) (PDLL). The side chains of each PL were modified with propylene oxide (PO) of different chiralities including (R)PO, (S)PO and (R,S)PO. These PL-POs with distinct chirality in main and side chains could condense pDNA into polyplexes. The polyplexes had approximately the same size, zeta potential and binding ability, but showed distinct gene transfection efficiency. We found that the PLs of L-configuration in the main chain had higher transfection efficiency than that of D or DL configuration due to their faster cellular uptake, while the side chain chirality had no effect on transfection efficiency.