Efficient in situ gene delivery via PEG diacrylate matrices

Area of Science:

• Biomaterials Science
• Gene Therapy
• Immunotherapy

Background:

• Cellular therapies for genetic disorders and cancer often require ex vivo cell modification.
• Therapy efficacy depends on gene expression and modified cell persistence.
• In situ gene delivery offers a promising alternative to minimize post-manipulation effects and systemic side effects.

Purpose of the Study:

• To develop and evaluate polyethylene (glycol) diacrylate (PEGDA) based cryogels for in situ localized gene delivery.
• To enhance cell adhesion and viral retention for improved gene transduction efficiency.
• To investigate the potential of these cryogels for immunotherapy and tissue engineering.

Main Methods:

• PEGDA cryogels were fabricated and modified by blending with gelatin methacrylate (GELMA) or surface modification with poly-l-lysine (PLL).
• In vitro experiments utilized lentiviruses encoding green fluorescent protein (GFP) to assess transduction efficiency in HEK 293FT cells.
• In vitro release studies evaluated viral retention, followed by in vivo gene delivery experiments.

Main Results:

• PEGDA-GELMA and PEGDA-PLL cryogels demonstrated significantly higher transduction efficiency compared to unmodified PEGDA cryogels.
• PEGDA-PLL cryogels exhibited improved retention of GFP lentiviruses.
• In vivo gene delivery using PEGDA-PLL cryogels outperformed bolus delivery via injection.

Conclusions:

• PEGDA-based cryogels, particularly PEGDA-PLL, represent a viable material platform for effective in situ gene delivery.
• These cryogels show promise for enhancing immunotherapy and have potential in broader tissue engineering applications.