Progress in gene targeting and gene therapy for retinitis pigmentosa
- Trinity College, Dublin (Ireland); and others
Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.
- OSTI ID:
- 134748
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1486
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
A novel mutation (ASn244Lys) in the peripherin/RDS gene causing autosomal dominant retinitis pigmentosa associated with bull's eye maculopathy detected by nonradioisotopic SSCP
Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21
Related Subjects
BASIC STUDIES
PATIENTS
SENSE ORGANS DISEASES
HEREDITARY DISEASES
GENES
BIOLOGICAL MODELS
GENE MUTATIONS
GENETIC MAPPING
DNA SEQUENCING
STRUCTURE-ACTIVITY RELATIONSHIPS
DETECTION
RHODOPSIN
HUMAN CHROMOSOME 3
HUMAN CHROMOSOME 6
TRANSGENIC MICE
THERAPY
GENE RECOMBINATION
DNA-CLONING
STEM CELLS
EMBRYONIC CELLS
ADENOVIRUS