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. 2019:1185:119-124.
doi: 10.1007/978-3-030-27378-1_20.

A Discovery with Potential to Revitalize Hammerhead Ribozyme Therapeutics for Treatment of Inherited Retinal Degenerations

Alexandria J Trujillo  1 , Jason M Myers  2 , Zahra S Fayazi  2 , Mark C Butler  2 , Jack M Sullivan  3   4   5   6
Affiliations

A Discovery with Potential to Revitalize Hammerhead Ribozyme Therapeutics for Treatment of Inherited Retinal Degenerations

Alexandria J Trujillo et al. Adv Exp Med Biol. 2019.

Abstract

Hammerhead ribozymes (hhRzs), RNA enzymes capable of site-specific cleavage of arbitrary target mRNAs, have faced significant hurdles in development and optimization as gene therapeutics for clinical translation. Chemical and biological barriers must be overcome to realize an effective therapeutic. A new Facilitated ribozyme has been identified with greatly enhanced kinetic properties that lead new insight on the capacity of ribozymes to target mutant genes to treat inherited retinal degenerations.

Keywords: Gene therapy; Hammerhead ribozyme; Inherited retinal degenerations; Noncoding RNA; RNA biologic therapies; Retinitis pigmentosa.

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Figures

Fig. 20.1
Fig. 20.1
Cleavage kinetics of minimal (hhRz266), F-hhRz266, F2-hhRz266, and F3-hhRz266. Data are from fluorescent cleavage assays against a short substrate in low magnesium and substrate in 10× excess to enzyme conditions. Cleavage of substrate alleviates FAM quenching causing a fluorescent signal. Right minimal hhRz, left F-hhRz. Green represents target with arrow site of cleavage
See this image and copyright information in PMC

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