Metabolite-Based Modification of Poly(l-lysine) for Improved Gene Delivery.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Synthetic gene delivery systems require multifunctional components for safe and effective DNA transport.
• Poly(l-lysine) (PLL) is a common gene delivery vector, but its efficiency and safety can be improved.

Purpose of the Study:

• To develop novel metabolite-based PLL modifiers imparting both pH buffering and nanoparticle stabilization.
• To evaluate the impact of these modifiers on the performance of PLL DNA nanoparticles.

Main Methods:

• Synthesized PLL modifiers based on morpholine (M), morpholine and niacin (MN), and thiomorpholine (TM).
• Assessed buffering capacity, nanoparticle stability, resistance to polyanion exchange, and blood circulation time.
• Evaluated in vitro transfection efficiency and cytotoxicity.
• Tested in vivo transfection in muscle tissue following intramuscular injection.

Main Results:

• PLL modification with MN or TM imparted pH buffering (pH 5-7) in solution and cells.
• Modified PLL nanoparticles showed enhanced stability, resistance to polyanion exchange, and prolonged blood circulation.
• In vitro transfection efficiency increased with reduced toxicity compared to unmodified PLL and PLL(M).
• PEG-PLL(MN) nanoparticles achieved sustained in vivo transfection in muscle tissue for over 45 days.

Conclusions:

• Metabolite-based PLL modifiers offer a dual-function approach to enhance synthetic gene delivery systems.
• These multifunctional units improve transfection efficiency and biocompatibility.
• The developed polymer modifiers represent a promising advancement in gene therapy vectors.