Cone Photoreceptor-Targeted Gene Therapy for Diseases of the Eye

Technology #13859

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Sanford L. Boye
William W. Hauswirth
Frank Dyka
Managed By
April Kilburn
Assistant Director 352-392-8929
Patent Protection
US Patent 9,375,491

AAV Vector and Chimeric Promoter Delivers Therapeutic Genes Selectively to Cone Photoreceptors to Treat Cone-Mediated Diseases

This AAV vector gene therapy targets all classes of cone photoreceptor cells by using a chimeric promoter sequence for treating cone-mediated disorders, including Achromatopsia, cone dystrophies and macular degeneration. It has been shown to rescue function and preserve cone photoreceptors in both small (mouse) and large (dog) animal models of Achromatopsia. Achromatopsia is characterized by the inability to see color, blindness in full sunlight, and decreased vision. In the United States, the hereditary disorder affects about 1 in every 33,000 people. Age-related macular degeneration affects 40 million people worldwide. Traditional methods of cone photoreceptor gene therapy fail to effectively treat all cone cells. Available methods are either unable to selectively target all classes of cone photoreceptor cells or are not small enough to accommodate DNA sequences of transgene. University of Florida researchers have developed a method of gene therapy that combines the use of AAV vectors with a chimeric promoter to efficiently and selectively target the expression of polynucleotides to cone photoreceptors. The chimeric promoter can drive expression of therapeutic or functional proteins that are absent, defective or underexpressed in cone cells. The gene therapy is particularly useful in providing a vehicle for the delivery of therapeutic genes to diseases that affect cone photoreceptors, such as Achromatopsia, cone dystrophies and may have future potential for treatment of age-related macular degeneration.


Gene therapy that targets cone photoreceptors to treat diseases of the eye


  • Selectively targets all cone photoreceptor classes S, M and L cones, offering treatment for Achromatopsia and other cone-mediated disorders
  • Small enough to accommodate large DNA sequences for use in AAV-mediated gene therapy, overcoming the obstacle of traditional methods.
  • Validated in dog models of Achromatopsia, which is often an indicator that human trials will yield similar results


In an effort to improve upon previous cone targeting promoters used in conjunction with AAV-mediated gene delivery, University of Florida researchers created a chimeric promoter for cone cell specific expression of a polynucleotide in a human or animal. In order to effectively and safely deliver genes to cone photoreceptors of affected individuals, gene therapy vectors must use promoters that drive transgene expression efficiently and selectively with no off-target expression in rod photoreceptors or other non-photoreceptor cell types. The promoter must be capable of driving gene expression in all subclasses of cone photoreceptors, and it must be small enough to accommodate transgene DNA. To date, cone-targeting promoters used in gene therapy are deficient in one or more of these criteria. Researchers created a chimeric promoter in which the sequence corresponding to the interphotoreceptor retinoid-binding protein gene was directly fused to the sequence of human cone transducing alpha-subunit. When incorporated into an AAV vector, tests of the resulting vector indicated that expression was limited to photoreceptors with no off-target expression observed. All cone receptors appear to be efficiently transduced, with some expression seen in rod photoreceptors. Additionally, AAV vectors incorporating this promoter have been used successfully in large and small animal models of Achromatopsia. Specifically, the promoter was combined with genes encoding either CNGB3 or CNGA3 and packaged in AAV vectors. Treatment with vector in CNGB3 deficient dogs, CNGB3 knock-out mice and CNGA3 deficient mice led to improvements in cone function and preservation over the long term.