TY - JOUR
T1 - Suppression of transthyretin expression by ribozymes
T2 - A possible therapy for familial amyloidotic polyneuropathy
AU - Tanaka, Kimihiro
AU - Yamada, Takeshi
AU - Ohyagi, Yasumasa
AU - Asahara, Hideaki
AU - Horiuchi, Izumi
AU - Kira, Jun ichi
N1 - Funding Information:
We thank Prof. Y. Sakaki (The University of Tokyo) for providing a human transthyretin cDNA, and Dr. T. Ohno (Riken Gene Bank) for permitting the use of HepG2 cells. We also thank Mr. M. Yoneda for preparing the manuscript. This study was supported, in part, by a grant from the Ministry of Health and Welfare of Japan.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - Familial amyloidotic polyneuropathy type 1 (FAP) is an autosomal-dominantly inherited disorder with systemic deposition of a variant transthyretin (TTR). We attempted to suppress TTR production by ribozyme degradation of TTR mRNA. Hammerhead and hairpin ribozymes cleaved TTR mRNA at specific individual sites in vitro. A ribozyme targeting a variant TTR (E61K) degraded the variant mRNA, but not a wild-type mRNA. These ribozymes also reduced the amounts of TTR mRNA and protein in HepG2 cells and COS-1 cells transfected with TTR-E61K cDNA. Ribozymes might be studied further as a potential treatment for FAP.
AB - Familial amyloidotic polyneuropathy type 1 (FAP) is an autosomal-dominantly inherited disorder with systemic deposition of a variant transthyretin (TTR). We attempted to suppress TTR production by ribozyme degradation of TTR mRNA. Hammerhead and hairpin ribozymes cleaved TTR mRNA at specific individual sites in vitro. A ribozyme targeting a variant TTR (E61K) degraded the variant mRNA, but not a wild-type mRNA. These ribozymes also reduced the amounts of TTR mRNA and protein in HepG2 cells and COS-1 cells transfected with TTR-E61K cDNA. Ribozymes might be studied further as a potential treatment for FAP.
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U2 - 10.1016/S0022-510X(00)00481-0
DO - 10.1016/S0022-510X(00)00481-0
M3 - Article
C2 - 11166799
AN - SCOPUS:0035862631
SN - 0022-510X
VL - 183
SP - 79
EP - 84
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1
ER -