Silencing of Amyloid Precursor Protein Expression Using a New Engineered Delta Ribozyme

Table 1

Determination of the most potential cleavage sites within APP mRNA.

Cleavage position	mRNA sequence^1; recognition domain/biosensor domain	Accessibility^2	SOFA-HDv Rz cleavage activity (%)^3
276	5′-GCACAUG/CCAGAAUGGGAA-3′	++	62
440	5′-GCAAGCG/GCAAGCAGUGCA-3′	+++	18
444	5′-GCGGGGC/GCAGUGCAAGAC-3′	+++	20
446	5′-GGGGCCG/AGUGCAAGACCC-3′	+++	26
459	5′-GUGCAAG/UCCCCACUUUGU-3′	+++	14
465	5′-GACCCAU/CUUUGUGAUUCC-3′	++	26
753	5′-GGAGGAU/GGAUGUCUGGUG-3′	++	36
756	5′-GGAUGAC/UGUCUGGUGGGG-3′	+	36
784	5′-GCAGACA/UAUGCAGAUGGG-3′	+	25
885	5′-GGACGAU/UGGUGAUGAGGU-3′	+	71

¹ The sequences of the mRNA bound by both the ribozyme’ recognition and biosensor domains. ² Accessibility of potential cleavage sites based on RNase H hydrolysis. ³ Percentage of cleavage activity of the various SOFA-HDV ribozymes targeting the APP mRNA.