TY - CHAP
T1 - Small Molecule-Based Inducible Gene Therapies for Retinal Degeneration
AU - Datta, Shyamtanu
AU - Peng, Hui
AU - Hulleman, John D.
N1 - Funding Information:
Acknowledgments This work was funded by the Roger and Dorothy Hirl Research Fund, a Career Development Award and unrestricted grant from Research to Prevent Blindness, and NIH grants R21EY028261, R01EY027785, and P30EY020799.
Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019
Y1 - 2019
N2 - The eye is an excellent target organ for gene therapy. It is physically isolated, easily accessible, immune-privileged, and postmitotic. Furthermore, potential gene therapies introduced into the eye can be evaluated by noninvasive methods such as fundoscopy, electroretinography, and optical coherence tomography. In the last two decades, great advances have been made in understanding the molecular underpinnings of retinal degenerative diseases. Building upon the development of modern techniques for gene delivery, many gene-based therapies have been effectively used to treat loss-of-function retinal diseases in mice and men. Significant effort has been invested into making gene delivery vehicles more efficient, less toxic, and non-immunogenic. However, one challenge for the treatment of more complex gain-of-function diseases, many of which might be benefited by the regulation of cellular stress-responsive signaling pathways, is the ability to control the strategy in a physiological (conditional) manner. This review is focused on promising retinal gene therapy strategies that rely on small molecule-based conditional regulation and the inherent limitations and challenges of these strategies that need to be addressed prior to their extensive use.
AB - The eye is an excellent target organ for gene therapy. It is physically isolated, easily accessible, immune-privileged, and postmitotic. Furthermore, potential gene therapies introduced into the eye can be evaluated by noninvasive methods such as fundoscopy, electroretinography, and optical coherence tomography. In the last two decades, great advances have been made in understanding the molecular underpinnings of retinal degenerative diseases. Building upon the development of modern techniques for gene delivery, many gene-based therapies have been effectively used to treat loss-of-function retinal diseases in mice and men. Significant effort has been invested into making gene delivery vehicles more efficient, less toxic, and non-immunogenic. However, one challenge for the treatment of more complex gain-of-function diseases, many of which might be benefited by the regulation of cellular stress-responsive signaling pathways, is the ability to control the strategy in a physiological (conditional) manner. This review is focused on promising retinal gene therapy strategies that rely on small molecule-based conditional regulation and the inherent limitations and challenges of these strategies that need to be addressed prior to their extensive use.
KW - Chemical biology
KW - Dihydrofolate reductase
KW - Gene therapy
KW - Retinal degeneration
KW - Small molecule-based conditional regulation
KW - Therapeutics
KW - Trimethoprim
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U2 - 10.1007/978-3-030-27378-1_11
DO - 10.1007/978-3-030-27378-1_11
M3 - Chapter
C2 - 31884590
AN - SCOPUS:85077313113
T3 - Advances in Experimental Medicine and Biology
SP - 65
EP - 69
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -