Document Type

Thesis

Degree

Master of Science (MS)

Department

Biomedical Engineering

First Advisor's Name

Wei-Chiang Lin

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Anthony J. McGoron

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Chenzhong Li

Third Advisor's Committee Title

Committee member

Keywords

cationic polymer, gene delivery, HEK 293

Date of Defense

11-18-2015

Abstract

Gene therapy involves the use of nucleic acids, either DNA or RNA for the treatment, cure, or prevention of human diseases. Synthetic cationic polymers are promising as a tool for gene delivery because of their high level of design flexibility for biomaterial construction and are capable of binding and condensing DNA through electrostatic interactions.

Our lab has developed a novel polymer (poly (polyethylene glycol-dodecanoate) (PEGD), a polyester of polyethylene glycol (PEG) and dodecanedioic acid (DDA). PEGD is a linear viscous polymer that self-assembles into a vesicle upon immersion in an aqueous solution. A copolymer of dodecanedioc acid and polyethylene glycol (PEG) was synthesized at a 1:1 ratio. Furmaric (FA) or itaconic acid (IA) was used to suppress DDA in the PEGD copolymer at an 80:20 ratio (DDA: furmaric/itaconic acid) to form the PEGDF/I variant. PEGDF/I are then modified through the Michael addition of Protamine Sulfate (PEGDF/I-PS) and Cys-Arg8 (PEGDF/I-CA) peptide to the carbon-carbon double bond on the polymer backbone to introduce a positive charge.

The modified PEGDF/I polymers were capable of binding and condensing DNA. Transfection of HEK 293 cells with pTurboGFP plasmid using modified PEGDF/I polymers was successful but showed varied efficiency. The PEGDF/I-CA polymer had around 30% transfection efficiency and was shown to be non-cytotoxic.

Identifier

FIDC000210

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