Abstract: A methodology for screening libraries of compounds for desirable biological/therapeutic activities, preferably using an automated system for the microinjection of compound(s) of interest into the open circulatory system (i.e., hemolymph) of Drosophila larvae genetically modified to sensitize a particular signaling pathway related to a human disease either by expression of a human disease gene or by the activation of a Drosophila gene that in the adult fly results in the development of an easily detectable phenotypes such that compounds that selectively interfere with this specific signaling pathway will modify or suppress the phenotype and can be identified rapidly and efficiently.
Abstract: A replication-defective recombinant virus, preferably an adenovirus that lacks E1a, E1b and E4 ORF 6, capable of infecting an eye and containing a ORF encoding a protein that when expressed in lens epithelial cells of an eye, suppresses, at the level of the germinative epithelium of the lens of the eye, cellular proliferation which is stimulated by eye surgery and which would otherwise result in secondary cataract formation in the eye is disclosed. The ORF, to be expressed, is under the control of a promoter sequence which is expressly exclusively in human lens epithelial cells. The preferred ORFs, to be expressed, include a non-phosphorylatable retinoblastoma ORF, a dominant negative mutant of a human RAS ORF and a Herpes thymidine kinase ORF.
Type:
Grant
Filed:
June 3, 1997
Date of Patent:
March 13, 2001
Assignee:
University of Lausanne
Inventors:
Phillip Herbert Shaw, Roland Sahli, Michel Sickenberg, Francis Munier