Design And Preparation Of Poly(L-lysine) Based Non-viral Gene Delivery Vectors

A series of high performance poly(L-lysine) based gene deliveryvectors are prepared and used for gene transfection in vitro. First, amultifunctional and electrically neutral polymer P(His-co-DMAEL) isprepared from lactose and histidine monomers by the reversibleaddition-fragmentation chain transfer (RAFT) polymerization. ThenP(His-co-DMAEL) is incorporated into PLL via two different strategies.One is the covalent grafting strategy, via which P(His-co-DMAEL) isgrafted to PLL to form PLL-g-P(His-co-DMAEL) conjugate. ThenPLL-g-P(His-co-DMAEL) conjugate condenses plasmid DNA (pDNA) toform PLL-g-P(His-co-DMAEL)/pDNA binary complexes. The otherstrategy is the non-electrostatic assembly strategy, via whichPLL-g-P(His-co-DMAEL) is assembled with pDNA and PLL to formPLL/pDNA/P(His-co-DMAEL) ternary complexes. With the samecontent of P(His-co-DMAEL) in the complexes, under various conditions,PLL-g-P(His-co-DMAEL)/pDNA and PLL/pDNA/P(His-co-DMAEL) complexes show obviously different complex stability， and thedifferences are related to the content of P(His-co-DMAEL). With lowercontent of P(His-co-DMAEL), the PLL-g-P(His-co-DMAEL)/pDNAbinary complexes show better complex stability than that with higherP(His-co-DMAEL) content. By contrary, in both cases,PLL/pDNA/P(His-co-DMAEL) ternary complexes show excellentcomplex stability. In vitro gene transfection shows that thePLL/pDNA/P(His-co-DMAEL) ternary complexes and thePLL-g-P(His-co-DMAEL)/pDNA binary complexes with lowP(His-co-DMAEL) content have very high gene transfection efficiencyunder both serum and serum free conditions. These results indicate thatP(His-co-DMAEL) modified PLL is a promising non-viral gene deliveryvector.