Retinal Drug/Gene Delivery
Member, Carolina Institute for NanoMedicine
Member, Lineberger Comprehensive Cancer Center
Gene and drug delivery for retinal diseases
Education and Training:
MD: Henan University School of Medicine
MS: Tongji Medical University
PhD: Huazhong University of Science & Technology
University of Florida (under Dr. Peter W Stacpoole): Gene therapy for mitochondrial genetic disease using AAV
University of Florida (under Dr. Arun Srivastava): Develop safe and effective recombinant parvovirus vectors for gene therapy
Nanoparticle-mediated large genomic DNA (gDNA) delivery for ocular diseases. The goal of gene therapy is for the delivered gene (transgene) to be expressed in a physiological manner. Current strategies use cDNA for gene targeting, but gDNA, which contains endogenous regulatory sequences, may better preserve the stability of the message and faithfully mimic the normal pattern of the natural gene expression. We utilize compacted DNA nanoparticles, which have the ability to transfer large genetic messages to compare the efficacy of cDNA in ameliorating retinal disease phenotypes in a retinitis pigmentosa model. Our results have shown that nanoparticles carrying rhodopsin gDNA locus present superior results compared with nanoparticles housing cDNA sequence only. We are working on defining the structural requirements for transgenes, including whether the full-length gDNA will faithfully recapitulate the expression profile, how the non-coding sequences will influence the expression of a gene, and whether the gDNA will argue for large expected changes in the phenotype of genetic diseases.
Developing novel nanoantioxidants for the treatment of age-related macular degeneration (AMD). There is growing evidence that both forms of AMD (dry & wet) are correlated with the elevated production of reactive oxygen species (ROS) caused by multifactorial pathological processes, including oxidative stress, inflammation, and angiogenesis. Nanoceria has been widely used as an anti-oxidant in various biomedical applications due to its auto-regenerative properties, which can continuously scavenge free radicals (also known as ROS). However, its potential to be used in biomedicine has been hampered by its water insolubility, which prevents its direct uptake by cells and reduces its efficacy and therapeutic index. We have synthesized a water soluble and stable nanoceria formulation using a chitosan derivative in plain water (U.S. Provisional Application No. 62/459,294). Our studies have shown promising antioxidant activity, anti-inflammatory, and anti-angiogenesis both in in vitro and in vivo AMD models, indicating the feasibility of using this system as an alternative and novel approach for AMD patients for whom standard options will not work or are not available. In addition, this project could be translatable numerically for treating several other diseases, such as neurodegenerative disorders, tumors, and diabetes, which are challenged by current standard approaches.
Developing injectable hydrogels for controlled release. It is well known that hydrogels are ideal biomaterials for cell culture and tissue engineering due to their tissue-like biocompatibility properties. Many retinal disorders, such as AMD and diabetic retinopathy, occur in chronic conditions, which may require long-term treatment. Currently, we are working on several biocompatible and biodegradable injectable hydrogels for delivering several types of therapeutic agents for sustained release. Using a prolonged release formulation reduces dosing frequency and increases the stability, safety, patient compliance, and convenience of administration. Properties of the injectable hydrogels are tunable and form as gel in situ after injection through thermosensitive or chemical crosslinking activities. Current active projects include injectable hydrogel formed nanocerias, Car-T cells and stem cells for AMD, retinoblastoma and diabetic retinopathy.
Designing and testing multifunctional nanoparticles. Another interest of our laboratory is to produce a multifunctional nanoparticle carrier for specific and efficient gene/drug targeting. We are developing a new nano-delivery system that has the capability of carrying multiple imaging, targeting, and therapeutic moieties to restore vision or to target tumors. We expect to build a smart molecularly engineered image-guided nanoparticle carrier capable of overcoming extracellular and intracellular barriers for delivering the therapeutic gene/drug to the desired cell population.
** A Han lab postdoctoral position is currently available. Interested candidates are invited to apply through the following link: https://unc.peopleadmin.com/postings/269554. **