Table 3.

Mutational alleles susceptible to hhRzs and potential to generate allelic variant WT opsin proteins.

Ribozyme	WT Sequence			Susceptible Mutations	aWT Sequence			Coding Mutation in aWT
hhRz 262	AAC	UUC↓	CUC	all but T58R	AAC	UUG	CUC	yes F56C
	N55	F56	L57		N55	C56	L57
hhRz 266	UUC	CUC↓	ACG	all but T58R	UUC	CUG	ACG	no
	F56	L57	T58		F56	L57	T58
hhRz 272	ACG	CUC↓	UAC	all but T58R	ACG	CUG	UAC	no
	T58	L59	Y60		T58	L59	Y60
hhRz 356	AUG	GUC↓	CUA	all but V87D and G89D	AUG	GUG	CUA	no
	M86	V87	L88		M86	V87	L88
Rz525/hhRz 485*	GUG	GUC↓	CUG	all but L131P	GUG	GUG	CUG	no
	V129	V130	L131		V129	V130	L131
hhRz 785	ACC	GUC↓	AAG	all	ACC	GUG	AAG	no
	T229	V230	K231		T229	V230	1 K231
hhRz 1197	ACC	UUC↓	CCC	all	ACC	UUG	CCC	no
	ϕ	ϕ	ϕ		ϕ	ϕ	ϕ
hhRz 1411	CAA	CUC↓	AUC	all	CAA	CUG	AUC	no
	ϕ	ϕ	ϕ		ϕ	ϕ	ϕ
hhRz 1414	CUC	AUC↓	UUU	all	CUC	AUG	UUU	no
	ϕ	ϕ	ϕ		ϕ	ϕ	ϕ

Cleavage site is shown in the WT sequence. ϕ indicates that the triplet targeted is in a noncoding mRNA region. The same cleavage site is attacked in most if not all known human rod opsin mutants (Susceptible Mutations). Conversion of NUH↓ to NUG creates a noncleavable site in an allelic variant cDNA and mRNA (aWT). Allelic variation to create a NUG site may promote a new mutation which could be deleterious to local or global protein structure or function (e.g. F56C in aWT for hhRz 262 would alter the primary sequence underlying the first transmembrane helix of rhodopsin). While cleavage potential is considered here there is also the potential for pure antisense effects. hhRzs in bold are lead candidate therapeutics.

^*Rz525/hhRz485is the lead candidate hhRz of Gorbatyuk et al (2007).