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Pharmacokinetics and transgene expression of implanted polyethylenimine-based pDNA complexes
Laura Rose1, Parvin Mahdipoor2, Cezary Kucharski2
1Department of Biomedical Engineering, Faculties of Medicine & Dentistry and Engineering, University of Alberta, Edmonton, AlbertaT6G 2G6 Canada.
Biomaterials Science
|February 2, 2016
Summary
Polyethylenimine-linoleic acid (PEI-LA) effectively delivers plasmid DNA (pDNA) for gene therapy, showing sustained transgene expression for 4 weeks in implants. This non-viral gene carrier demonstrates promise for regenerative medicine applications.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Regenerative Medicine
Background:
- Locally delivered plasmid DNA (pDNA) holds potential for regenerative medicine, but in situ pharmacokinetics and transgene expression data in animal models are limited.
- Understanding pDNA behavior within implants is crucial for developing effective gene-based therapies.
Purpose of the Study:
- To investigate the in situ pharmacokinetics and transgene expression of locally delivered pDNA using polyethylenimine (PEI) and PEI-linoleic acid (PEI-LA) in a rat subcutaneous implant model.
- To evaluate the efficacy of PEI and PEI-LA as non-viral gene carriers for sustained gene delivery in implants.
Main Methods:
- Developed and validated an efficient pDNA extraction and quantitative PCR (qPCR) method for assessing pDNA in gelatin sponge implants.
- Compared the retention and transfection efficiency of naked pDNA, PEI-pDNA complexes, and PEI-LA-pDNA complexes in vivo.
- Utilized a reporter gene (DsRed) to monitor mRNA and protein expression following pDNA delivery.
Main Results:
- Naked pDNA was rapidly lost (>98% within 24 hours), while PEI- and PEI-LA-delivered pDNA remained intact for 2 and 4 weeks, respectively.
- Only PEI-LA mediated significant mRNA and protein expression, despite both PEI and PEI-LA complexes being internalized by cells.
- Sustained mRNA expression for at least 4 weeks was observed with PEI-LA, correlating with pDNA retention in implants.
Conclusions:
- PEI-LA is an effective non-viral gene carrier for sustained pDNA delivery and transgene expression in implants.
- This study provides critical insights into the in situ pharmacokinetics and gene expression of implanted non-viral gene carriers, supporting their development for regenerative medicine.
