Synthetic Helical Polypeptide as a Gene Transfection Enhancer

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gene Delivery Systems

Background:

• Low transfection efficiency of polymeric gene carriers hinders their therapeutic applications.
• A universal and simple strategy is needed to enhance gene delivery efficacy.

Purpose of the Study:

• To develop a novel cationic polypeptide, poly(γ-aminoethylthiopropyl-l-glutamate) (PALG-MEA), to improve gene transfection efficiency.
• To demonstrate the broad applicability of this strategy across various cationic polymers and gene delivery systems.

Main Methods:

• Synthesis of poly(γ-aminoethylthiopropyl-l-glutamate) (PALG-MEA) with a stable α-helical conformation.
• Noncovalent integration of PALG-MEA into existing polymeric gene delivery systems via electrostatic interactions.
• Evaluation of cellular uptake, endosomal escape, and transfection efficiency in vitro and in vivo.
• Assessment of the system's efficacy in delivering gene editing components (sgRNA-Cas9 plasmids).

Main Results:

• PALG-MEA significantly enhanced gene transfection efficiency of cationic polymers.
• The enhanced systems showed improved cellular uptake and endosomal escape.
• The strategy was effective with various cationic polymers including PEI, PLL, and PAMAM.
• A ternary system (PM/pshVEGF/PEI) demonstrated potent antitumor effects in a B16F10 tumor model.
• PALG-MEA also improved the delivery of gene editing systems.

Conclusions:

• Poly(γ-aminoethylthiopropyl-l-glutamate) (PALG-MEA) offers a facile and effective strategy to enhance polymeric gene delivery systems.
• This approach improves transfection efficiency, cellular uptake, and endosomal escape.
• The developed system shows promise for both gene therapy and gene editing applications.