| Project/Area Number |
11670736
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | TOHOKU UNIVERSITY |
|---|
Principal Investigator |
MATSUBARA Yoichi TOHOKU UNIV, MEDICAL GENETICS, PROFESSOR, 大学院・医学系研究科, 教授 (00209602)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoichi TOHOKU UNIV, MEDICAL GENETICS, ASSOCIATE RESEARCHER, 大学院・医学系研究科, 助手 (80216457)
KURE Shigeo TOHOKU UNIV, MEDICAL GENETICS, ASSOCIATE PROFESSOR, 大学院・医学系研究科, 助教授 (10205221)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | Phenylketonuria / Gene therapy / Adenovirus / TaqMan-PCR / Tetrahydrobiopterin / Fetal gene therapy |
|---|
| Research Abstract |
We first tested the feasibility of targeted gene correction using chimeric DNA/RNA oligonucleotide in phenylketonuria mutations. However, we failed to observe efficient nucleotide substitution as reported by Kimeragen in U.S.A.Although it seems important to characterize various parameters affecting mismatch repair mechanism and further optimize the method, our observation as well as other's might throw doubt upon the credibility of the previous reports.
In contrast, gene transfer experiments using recombinant adenovirus obtained following fruitful results : 1) a strong host immune reaction was demonstrated against extrinsic phenylalanine hydroxylase, rather than adenovirus per se ; 2) a pharmacological dose of tetrahydrobiopterin, a cofactor for phenylalanine hydroxylase, appeared to enhance the enzymatic activity after gene therapy ; 3) an efficient gene transfer method to fetus was established in an animal model ; 4) a TaqMan-PCR method to quantify adenoviral particles in tissues was developed. Our study will facilitate the clinical application of gene therapy in inborn errors of metabolism caused by hepatic enzyme deficiency.
|
