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Gene therapy for red–green colour blindness in adult primates


Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.

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Figure 1: rAAV2/5 vector produced functional L-opsin in primate retina.
Figure 2: Pre-therapy colour vision and possible treatment outcomes.
Figure 3: Gene therapy produced trichromatic colour vision.


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This work was supported by the National Institutes of Health grants R01EY016861 (M.N.) and R01EY11123 (W.W.H.); Research Training Program in Vision Science Grant T32EY014537; NEI Core Grants for Vision Research P30EY01931, P30EY01730 and P30EY08571; the Harry J. Heeb Foundation, the Posner Foundation, the Macular Vision Research Foundation, the Foundation Fighting Blindness, Hope for Vision, and Research to Prevent Blindness. We would like to thank V. Chiodo, S. Boye, D. Conklyn, P. M. Summerfelt, K. Chmielewski and K. L. Gunther for technical assistance. J.N. is the Bishop Professor in Ophthalmology, M.N. is the Ray Hill Professor in Ophthalmology, and W.W.H. is Rybaczki-Bullard Professor of Ophthalmology.

Author Contributions Experiments and data analysis were performed by K.M., T.B.C., J.A.K., M.C.M., J.N. and M.N. Cone-specific expression of the gene therapy vector was developed and validated by Q.L., and W.W.H. constructed the vector and packaged it into adeno-associated virus and provided dosage guidance. All authors contributed to data interpretation. The manuscript was written by K.M., J.N. and M.N. and incorporates comments by all others.

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Correspondence to Jay Neitz.

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W.W.H. and the University of Florida have a financial interest in the use of AAV therapies and own equity in the company, Applied Genetic Technologies Corporation Inc. (Alachua, Florida).

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Mancuso, K., Hauswirth, W., Li, Q. et al. Gene therapy for red–green colour blindness in adult primates. Nature 461, 784–787 (2009).

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