Abstract
The ability to temporally control levels of a therapeutic protein in vivo is vital for the development of safe and efficacious gene therapy treatments for autosomal dominant or complex retinal diseases, where uncontrolled transgene overexpression may lead to deleterious off-target effects and accelerated disease progression. While numerous platforms exist that allow for modulation of gene expression levels – ranging from inducible promoters to destabilizing domains – many have drawbacks that make them less than ideal for use in recombinant adeno-associated virus (rAAV) vectors, which over the past two decades have become the mainstay technology for mediating gene delivery to the retina. Herein, we discuss the advantages and disadvantages of three major gene expression platforms with regard to their suitability for ocular gene therapy applications.
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Lipinski, D.M. (2019). A Comparison of Inducible Gene Expression Platforms: Implications for Recombinant Adeno-Associated Virus (rAAV) Vector-Mediated Ocular Gene Therapy. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_13
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DOI: https://doi.org/10.1007/978-3-030-27378-1_13
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