Effect of peptides and their introduction methods on target gene transfer of gene vector based on disulfide-containing polyethyleneimine.

To evaluate the effect of different peptides as well as their introduction methods on target gene transfer of gene vectors based on disulfide-containing polyethyleneimine (SS-PEI), a series of peptides including N(3)-GRGDSF, GRGDSF, and EEEEEEEEGRGDSF (E(8)GRGDSF) were prepared. N(3)-GRGDSF was conjugated to SS-PEI by click chemistry and SS-PEI-GRGDSF was obtained. GRGDSF was non-covalently introduced into SS-PEI/DNA mainly through hydrogen bonding to obtain SS-PEI/DNA/GRGDSF complexes, whereas E(8)GRGDSF was further non-covalently introduced to SS-PEI/DNA through electrostatic force to obtain SS-PEI/DNA/E(8)GRGDSF complexes.

Poly(β-amino amine) cross-linked PEIs as highly efficient gene vectors.

To increase the release of DNA into the cytoplasm and further improve transgene expression of nucleic acid novel polymeric gene carriers were prepared which would be biodegradable under the reducing conditions in the cytoplasm. Disulfide-containing poly(β-amino amine)s were first synthesized and then used to cross-link low molecular weight polyethyleneimine (1800 Da) through Michael addition to obtain SS-PBAA-PEIs as the final gene carriers. The physicochemical characteristics of SS-PBAA-PEI/DNA complexes were characterized.

Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei.

Cellular uptake and nuclear localization are two barriers to gene delivery. Here, we designed new gene delivery carriers with an N-terminal stearylated (STR) nuclear localization signal (NLS), PKKKRKV, present in the Simian Virus 40 large T antigen with the aim to overcome limitations, such as cell membrane and nuclear pores, offering attractive possibilities to enhance gene delivery. Four vectors with different structures of N-stearylated nuclear localization signal-octaarginine peptide (STR-PKKKRKV-R(8) or STR-NLS-R(8), STR-VKRKKKP-R(8) or STR-reverse NLS-R(8), PKKKRKV-R(8) or NLS-R(8), and VKRKKKP-R(8) or reverse NLS-R(8)) were compared.