Zongchao Han, Ph.D., M.D.

Assistant Professor

Member, Carolina Institute for NanoMedicine                     Zongchao Han, PhD, MD
Member, Lineberger Comprehensive Cancer Center

Specialty:          

Gene Therapy for Retinal Disease

Education and Training:

MD:

Henan University School of Medicine

MS:

Tongji Medical University

PhD:

Huazhong University of Science & Technology – Tongji Medical College

Postdoctoral Fellowships:

University of Florida (under Dr. Peter W Stacpoole): Gene Therapy for mitochondrial genetic disease using AAV
University of Florida (under Dr. Arun Srivastava): To   develop safe and effective recombinant parvovirus vectors for gene therapy

Research Goals:

NP-mediated large genomic DNA (gDNA) delivery for ocular diseases. The efficacy of gene therapy depends on the delivered gene (trans-gene) 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 normal gene regulation. We utilize compacted DNA nanoparticles which have the ability to transfer large genetic messages to compare the efficacy of cDNA vs. gDNA in ameliorating retinal disease phenotypes in a retinitis pigmentosa model. Our results show that NPs carrying a gDNA locus present superior results than NPs housing cDNA sequence only. We are working on defining the structural requirements for gene expression and how to express the trans-gene in the correct cellular address and in the correct amount.

Gene-based ‘surgery’ for ocular disorders. Conventional gene therapy focuses on “targeting-specific genes and/or gene supplementation” that supplies a therapeutic genetic material (i.e., virus-mediated wild-type cDNA transduction or knockdown).  An ideal approach for cure genetic disorders would be to correct defective genes that lead to disease at endogenous chromosomal locus, therefore, the defect in the chromosomal gene could be permanently repaired. This radical gene therapy approach will eliminate the need for multiple gene therapy strategies to address issues that are specific to mutations that have gain-of-function or dominant-negative effects. Our lab is working on novel gene-correction technology using TALEN and CRISPR for targeted gene correction in ocular genetic mouse models. We are using these new technologies to develop novel protocols and tools for targeted gene therapy of a variety of genetic ocular animal disorders.

Gene targeting diabetic retinopathy (DR): another of our interests is to prevent high glucose-induced increased vascular and neuronal complications associated with the development and progression of DR. Retinal neovascularization and choroidal neovascularization are two main causes for the vision loss in DR. The two vascular beds within the eye differ substantially in the characteristics of their surrounding cells. We use both AAV and NP as delivery vehicles and deliver genes encoding natural neurotrophic factor and/or in combination with a microRNA targeting system to diabetic animals either via subretinal or intravitreal injection.  Our goal is to determine the best route of gene delivery to achieve inhibition of neovascularization either in the retina or in the choroid.