This technology utilizes a DNA-templated micelle platform to selectively target the delivery of therapeutic drugs and genes to a wide range of cells.
Unmet Need: Consistent and efficient delivery of multiple therapeutic agents
Currently used nanoparticles can be formed into nanocarriers or conjugated to ligands for the delivery of chemotherapeutic agents. However, as nanomedicine becomes an emerging field in cancer treatment, the development of safe and consistent delivery platforms has become a prominent challenge. The use of nanocarriers poses a threat of nanotoxicity, in addition to inconsistent batch effects. Furthermore, concerns over loss of drug efficacy during encapsulation and delivery limit the scalability of the technology. As a result, there is continued demand for methods to effectively co-deliver multiple therapeutic cargo.
The Technology: Nanoparticle micelle platform for efficient delivery of multiple therapeutic agents
This platform implements DNA templates ligated to amine-functionalized polyethylene glycol (PEG) segments in order to form nanoparticle-sized micelles capable of efficiently delivering small nucleic acids and therapeutic drugs to target cells. The DNA bridge serves as modifiable template that can load a siRNA, gRNA, mRNA, or chemodrugs of interest, while the micelles can be conjugated with a customizable targeting peptide. The use of the DNA template allows not only heterogeneity within the micelle to carry multiple delivery agents, but also permits enhanced control over micelle formation, reducing the polydispersity and inconsistent batch effects.
This technology has been validated in vitro in cell lines and tumors.
Applications:
- Transfection method for in vitro cell lines
- Delivery platform for CRISPR/cas9 system
- Delivery platform for therapeutic drugs and small nucleic acids
- Treatment method for cancer and heterogeneous tumors
- Research tool for targeting specific cell types
Advantages:
- Allows co-delivery of multiple therapeutic agents
- Compatible with multiple cargoes including mRNA, gRNA, siRNA, miRNA, PNA, DNAzyme, antisense nucleotides, and therapeutic drugs
- Enhances control over nanoparticle micelle formation reducing polydispersity
- Enhances consistency between batches
- Easily customizable
- Enhances efficacy
- Reduces unwanted cytotoxicity
Lead Inventor:
Kam W. Leong, Ph.D.
Patent Information:
Patent Pending
Related Publications:
Lao YH, Li M, Gao MA, Shao D, Chi CW, Huang D, Chakraborty S, Ho TC, Jiang W, Wang HX, Wang S, Leong KW. “HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute” Advanced Science. 2018 May 18.
Zhang J, Li J, Shi Z, Yang Y, Xie X, Lee SM, Wang Y, Leong KW, Chen M. “pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities” Acta Biomaterialia. 2017 Aug; 58: 349-364.
Sun TM, Du JZ, Yao YD, Mao CQ, Dou S, Huang SY, Zhang PZ, Leong KW, Song EW, Wang J. “Simultaneous Delivery of siRNA and Paclitaxel via a ‘Two-in-One’ Micelleplex Promotes Synergistic Tumor Suppression” ACS Nano. 2011 Jan 4; 5(2): 1483-1494.
Leong KW, Maoa HQ, Truong-Leb VL, Roya K, Walsha SM, Augustb JT. “DNA-polycation nanospheres as non-viral gene delivery vehicles” Journal of Controlled Release. 1998 Apr 30; 53(1-3): 183-193.
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