| | |  | | | | Record from Web of Science® | | | | | | |
| A mutation-independent therapeutic strategem for osteogenesis imperfecta |
|
|
| Author(s): Millington-Ward S, O'Neill B, Kiang AS, Humphries P, Kenna PF, Farrar GJ |
| Source: ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT Volume: 9 Issue: 6 Pages: 537-542 Published: DEC 1999 |
| Times Cited: 17 References: 31 |
| Abstract: Given the genetically heterogeneous nature of many dominantly inherited disorders, it will be imperative to design mutation-independent therapeutic strategies to circumvent such heterogeneity. Intragenic polymorphism represents a genomic resource that may be harnessed in the development of allele-specific mutation-independent therapeutics. A hammerhead ribozyme, Rzpol1a1, selectively cleaves a common single-nucleotide polymorphism (SNP) of the human COL1A1 transcript (heterozygosity frequency of 2 pq = 0.4032, from Hardy-Weinberg equilibrium), One SNP variant contains a hammerhead ribozyme cleavage site, and the other does not. Kinetic evaluation shows Rzpol1a1 to be both specific and extremely efficient in vitro. Thus, a single efficient ribozyme has been characterized that should be valuable in the development of a gene therapy suitable for up to 1 in 5 dominant-negative osteogenesis imperfecta (OI) patients, where over 150 different mutations have been identified to date. Given the increasing characterization of intragenic SNP, it is predicted that such a mutation-independent strategy, based on selective silencing of mutant alleles at SNP, may become increasingly important in future genomics-driven drug development for many heterogeneous dominant disorders and complex traits. |
| Document Type: Article |
| Language: English |
| Reprint Address: Millington-Ward, S (reprint author), Univ Dublin Trinity Coll, Ocular Genet Unit, Dept Genet, Dublin 2, Ireland |
Addresses:
1. Univ Dublin Trinity Coll, Ocular Genet Unit, Dept Genet, Dublin 2, Ireland |
| Publisher: MARY ANN LIEBERT INC PUBL, 2 MADISON AVENUE, LARCHMONT, NY 10538 USA |
| Subject Category: Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental |
| IDS Number: 270XA |
| ISSN: 1087-2906 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |