Project Title: Molecular Engineering of Novel Adeno-Associated Virant Variants for the Transduction of Müller Cells (in collaboration with the Schaffer Lab)

Project Description:

Numerous retinal diseases, such as retinitis pigmentosa, glaucoma, and age-related macular degeneration (AMD), afflict millions of individuals worldwide, leading to progressive and irreversible blindness. Neuronal cell death, either in retinal ganglion cells or photoreceptors, ultimately underlies the pathophysiology of each of these conditions. Biomedical strategies that focus on the delivery of neuroprotective factors to afflicted areas using gene therapeutic techniques present a promising approach for the treatment of these disorders.

For retinal gene therapy, retinal-spanning Müller glial cells would be an ideal target for the sustained production and secretion of neuroprotective factors, such as glial-derived neurotrophic factor and fibroblast growth factor-2, which have previously been shown to slow down neuronal cell death in the retina. However, current viral vectors are ineffective in transducing this cell type via intravitreal injection.  Lentiviral vectors have shown Müller-permissivity via a subretinal injection route, but because of the invasiveness of this technique, intravitreal-administered vectors would be more clinically promising for treating retinal disorders.

My research focuses on engineering adeno-associated viral vectors for the modification of viral tropism to enhance specific transduction of Müller cells intravitreally.

Ryan Klimczak

Present - Ph.D. Candidate (MCB)

2004 - AB Biochemistry

Harvard University