Hybrid biosynthetic gene therapy vector development and dual engineering capacity

Area of Science:

• Immunology
• Biomaterials Science
• Molecular Biology

Background:

• Gene vaccines rely on effective gene delivery to immune cells.
• Antigen-presenting cells (APCs) are crucial for initiating immune responses.
• Current gene delivery vectors face challenges in cellular uptake, endosomal escape, and intracellular concentration.

Purpose of the Study:

• To develop and evaluate a hybrid gene delivery vector with both biological and biomaterial components.
• To overcome barriers in APC gene delivery, including cellular uptake and intracellular processing.
• To engineer a versatile platform for gene delivery immunotherapy.

Main Methods:

• Constructed a hybrid vector with an Escherichia coli inner core and a poly(beta-amino ester) outer coating.
• Utilized principles from molecular biology and polymer chemistry for vector design.
• Assessed in vitro gene delivery efficiency and in vivo immune response.

Main Results:

• The hybrid vector demonstrated enhanced in vitro gene delivery compared to individual components and commercial agents.
• Achieved improved cellular uptake, phagosomal escape, and intracellular cargo concentration in APCs.
• Showcased a potent, efficient, and safe in vivo humoral immune response.

Conclusions:

• The hybrid gene delivery vector offers a flexible and synergistic approach for immunotherapy.
• This platform enables multivariate engineering for advanced gene delivery applications.
• The design represents a significant advancement in overcoming APC gene delivery challenges.