Highly Stable Biodegradable Gene Vector Platforms for Overcoming Biological Barriers
Patent Number: WO2015175545A1
Executive Summary:
General Description:
A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems, capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.
Scientific Progress:
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal status: Pending
Publication PMID: 26680637, 28694032, 26124127, 25761435
Publications:
Mastorakos P, Zhang C, Song E, Kim YE, Park HW, Berry S, Choi WK, Hanes J, Suk JS. Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors. J Control Release. 2017 Sep 28;262:37-46.
Mastorakos P, Song E, Zhang C, Berry S, Park HW, Kim YE, Park JS, Lee S, Suk JS, Hanes J. Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. Small. 2016 Feb 3;12(5):678-85.
Mastorakos P, da Silva AL, Chisholm J, Song E, Choi WK, Boyle MP, Morales MM, Hanes J, Suk JS. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8720-5.
Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J. Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain. Adv Healthc Mater. 2015 May;4(7):1023-33.
Inventor Bio: Justin Hanes
https://cnm-hopkins.org/justin-hanes-phd/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/WO2015175545A1
- Research Institute: Johns Hopkins University
- Disease Focus: Gliomas, including Glioblastoma
- Basis of Invention: Highly stable PEG-based gene delivery vehicle capable of penetrating physiological barriers
- How it works: Gene therapy is a promising and potentially lucrative therapy for treating many kinds of diseases. A major obstacle for gene therapy is the delivery of the genes to the target tissues. For example, many gene delivery vectors are not able to penetrate the brain due to the blood-brain barrier. This invention overcomes this obstacle by using a novel PEG-based gene vector for delivery of genes to targets containing impenetrable biological barriers
- Lead Challenge Inventor: Justin Hanes
- Inventors: Justin Hanes, Jung Soo Suk, Panagiotis Mastorakos
- Development Stage: Preclinical
- Novelty:
- Methods for formulating gene vector
- Methods for using gene vector for delivery to targets with biological barriers
- Clinical Applications:
- Gene therapy
General Description:
A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Colloidally stable non-viral gene vector delivery systems, capable of overcoming various biological barriers, are disclosed. The gene vectors are biodegradable, non-toxic and highly tailorable for use in specific applications. The vectors include a mixture of biodegradable copolymers, such as PBAE, and biodegradable polymers conjugated with hydrophilic, neutrally charged polymer, such as PEG. The gene vectors demonstrate broad vector distribution and high transgene delivery in vivo, providing an efficient non-viral gene delivery system for localized therapeutic gene transfer. Methods of using the vectors to overcome biological barriers including mucus gel and extracellular matrix are provided. Methods of formulating the vectors are also provided.
Scientific Progress:
- Validation of gene delivery and transgene expression in vivo
- Characterization gene vector in vitro and in vivo
Future Directions:
- Clinical validation
Strengths:
- Good biochemical properties
- Efficient gene delivery and able to overcome biological barriers
- Stable and Biodegradable
- Scalable and rapid synthesis
Weaknesses:
- Not yet tested in humans
- Competition with other gene delivery systems (both viral and non-viral)
Patent Status:
Legal status: Pending
- Priority date: 2014-05-12
- Filing date: 2015-05-12
- Publication date: 2015-11-19
Publication PMID: 26680637, 28694032, 26124127, 25761435
Publications:
Mastorakos P, Zhang C, Song E, Kim YE, Park HW, Berry S, Choi WK, Hanes J, Suk JS. Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors. J Control Release. 2017 Sep 28;262:37-46.
Mastorakos P, Song E, Zhang C, Berry S, Park HW, Kim YE, Park JS, Lee S, Suk JS, Hanes J. Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. Small. 2016 Feb 3;12(5):678-85.
Mastorakos P, da Silva AL, Chisholm J, Song E, Choi WK, Boyle MP, Morales MM, Hanes J, Suk JS. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8720-5.
Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J. Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain. Adv Healthc Mater. 2015 May;4(7):1023-33.
Inventor Bio: Justin Hanes
https://cnm-hopkins.org/justin-hanes-phd/
