A small catalytic DNA molecule targeting c-myc RNA was found to be a potent
inhibitor of smooth muscle cell (SMC) proliferation. The catalytic domain
of this molecule was based on that previously derived by in vitro selection
(Santoro, S, W,, and Joyce, G, F, (1997) Proc. Natl, Acad. Sci. U.S.A. 94,
4262-4266) and is known as the "10-23" general purpose RNA-cleaving deoxyr
ibozyme, In addition to inhibiting SMC proliferation at low concentration,
this molecule (targeting the translation initiation region of c-myc RNA) wa
s found to efficiently cleave its full-length substrate in vitro and downre
gulate c-myc gene expression in smooth muscle cells. The serum nuclease sta
bility of this molecule was enhanced without substantial loss of kinetic ef
ficiency by inclusion of a 3'-3'-internucleotide inversion at the 3'-termin
al. The extent of SMC suppression was found to be influenced by the length
of the substrate binding arms. This correlated to some extent with catalyti
c activity in both the short substrate under multiple turnover conditions a
nd the full-length substrate under single turnover conditions, with the 9 9 base arm molecule producing the greatest activity.