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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
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Gene Delivery Mediated by Backbone-Degradable RAFT Copolymers
Prajakatta B Mulay1, D Christopher Radford1, Brayan Rondon2
1Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
Biomacromolecules
|February 12, 2026
Summary
Developing backbone-degradable cationic copolymers significantly enhances gene delivery efficiency and biocompatibility. These novel polymers show a 10-fold increase in transfection without added cytotoxicity, offering a promising gene delivery platform.
Area of Science:
- Polymer Chemistry
- Biotechnology
- Molecular Biology
Background:
- Cationic polymers are promising for gene delivery but often exhibit cytotoxicity.
- A need exists for biocompatible and effective polymeric gene delivery systems.
- Recent polymer chemistry advances enable the creation of degradable polymers.
Purpose of the Study:
- To develop backbone-degradable cationic copolymers for gene delivery.
- To evaluate the biocompatibility and efficacy of these novel polymers.
- To investigate the impact of backbone degradability on gene delivery performance.
Main Methods:
- Synthesized polycations via copolymerization with macrocyclic allylic sulfides using PET-RAFT polymerization.
- Created a library of copolymers with varying backbone degradability.
- Assessed transfection efficiency and cytotoxicity using a GFP plasmid in U-2 OS cells.
Main Results:
- Incorporation of degradable groups improved transfection efficiency by 10-fold at low N/P ratios.
- No increase in cytotoxicity was observed with the degradable copolymers.
- Enhanced gene delivery performance was achieved without compromising biocompatibility.
Conclusions:
- Backbone-degradable cationic copolymers represent a significant advancement in gene delivery.
- Degradability enhances gene delivery efficacy and maintains biocompatibility.
- These polymers offer a superior platform for gene therapy applications.
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