Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1997-07-16
1999-03-09
LeGuyader, John L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 231, 536 232, 435 6, 435 9131, 435375, C07H 2104
Patent
active
058802770
ABSTRACT:
The steroid enzyme 5.alpha.-reductase is responsible for the conversion of testosterone to the more-potent androgen dihydrotestosterone (DHT). The catalytic cleavage of nucleic acid encoding 5.alpha.-reductase by a ribozyme which selectively recognizes such nucleic acid reduces the level of expression of 5.alpha.-reductase by mammalian cells including human cells treated with such ribozyme. The reduction of nucleic acid (e.g. mRNA) levels leads to a corresponding reduction of enzyme levels and dihydrotestosterone levels in surrounding tissues, thus providing a therapeutic effect. The transformation of 5.alpha.-reductase producing cells with an expression vector containing a structural gene for a ribozyme is shown to decrease 5.alpha.-reductase expression. Pharmaceutical compositions and methods useful for topically administering effective amounts of such a ribozyme to hair follicle cells also are exemplified.
REFERENCES:
Rossi et al. AIDS Res. & Human Retrovirus. 8:183, (1992).
Stull et al. Pharm. Res. 12:465, (1995).
Andersson, S. et al., Proc. Natl. Acad. Sci. USA, 87:3640-3644 (May 1990).
Bratty, J. et al., Biochimica et Biophysica Acta., 1216:345-359 (1993).
Friedmann, T., Science, 244:1275-1281 (Jun. 1989).
Gao, L. et al., Human Gene Therapy, 4:17-24 (1993).
Gaston, K. et al., Nucleic Acids Research, 20 (No. 23):6297-6301 (1992).
Haseloff, J. et al., Nature, 334:585-591 (Aug. 1988).
Kashani-Sabet, M. et al., Antisense Research and Development, 2:3-15 (1992).
Labrie, F. et al., Endocrinology, 131 (No. 3):1571-1573 (1992).
Philip, R. et al., Molecular and Cellular Biology, 14 (No. 4):2411-2418 (Apr. 1994).
Synder, D. et al., Blood, 82 (No. 2):600-605 (Jul. 1993).
Taylor, N. et al., Nucleic Acids Research, 20 (No. 17):4559-4565 (1992).
Zhu, N. et al., Science, 261:209-211 (Jul. 1993).
Harris, G., et al., Proc. Natl. Acad. Sci. USA, 89:10787-10791 (1992).
Suwaya, M., Dermatology, Progress & Perspectives: Proceedings of the 18th World Congress of Dermatology, pp. 202-203 (1992).
McConnell, J., et al., J. Clin. Endocrinol. Metab., 74(No. 3):505-508 (1992).
Andersson, S., et al., Nature, 354:159-161 (1991).
Cunha, G., et al., Endocr. Rev., 8(No. 3):338-362 (1987).
Mooradian, A., et al., Endocr. Rev., 8(No. 1):1-28 (1987).
Cech, T., et al., Ann. Rev. Biochem., 55:599-629 (1986).
Cunliffe, W., et al., The Lancet, 1:685-687 (1969).
Hamilton, J., Am. J. Anat., 71:451-480 (1942).
M. Kashani-Sabet et al., "Application of ribozymes to cancer gene therapy," Cancer Gene Therapy, vol. 2, No. 3, 1995, pp. 213-223.
K. Scanlon et al., "Ribozyme-mediated reversal of the multidrug-resistant phenotype," Proc. Natl. Acad. Sci. USA, vol. 91, pp. 11123-11127, Nov. 1994.
H. Kobayashi et al., "Reversal of Drug Sensitivity in Multidrug-Resistant Tumor Cells by an MDRI (PGY1) Ribozyme," Cancer Research, 54:1271-1275, Mar. 1, 1994.
J. Ohkawa et al., "Importance of independence in ribozyme reactions: Kinetic behavior of trimmed and of simply connected multiple ribozymes with potential activity against human immunodeficiency virus," Proc. Natl. Acad. Sci. USA, vol. 90, pp. 11302-11306, Dec. 1993.
Kashani-Sabet Mohammed
Scanlon Kevin J.
City of Hope
LeGuyader John L.
The Regents of the University of California
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