| Project/Area Number |
13558094
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Toyama Medical and Pharmaceutical University |
|---|
Principal Investigator |
SHIRAKI Kimiyasu Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Virology, Professor, 医学部, 教授 (50135745)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Masahiko Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Virology, Associate Professor, 医学部, 助教授(前) (80186527)
|
|---|
| Project Period (FY) |
2001 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
|
|---|
| Keywords | Herpes simplex virus / Viral vector / attenuated vector / neurological function / gene therapy / anterior horn motor neuron / ウイルスベクター / 中枢神経系 / 潜伏感染 / 単純ヘルペスウイルスベクター / 脊髄前角運動細胞 / 神経親和性 / 弱毒ウイルス / 遺伝子発現ベクター |
|---|
| Research Abstract |
We have developed a live attenuated HSV-1 vector, βH1, expressing β-galactosidase (β-gal) in the nervous system. Its subcutaneous inoculation led the expression of β-gal activity in neurons of the sensory ganglia innervating the inoculation site for at least 45 days. βH1 was also sufficient to deliver the foreign gene into motor neurons in the bilateral anterior horn of the spinal cord of rats by an intramuscular inoculation and β-gal expression continued for at least 182 days in 90% of motor neurons in the bilateral anterior horn of spinal cord in a wide range. The presence of immunity to HSV was not an obstacle to deliver the transgene in anterior horn motor neurons in the intramuscularly inoculated rats. Furthermore, βH1 inoculation into the right caudate putamen of rats was efficient in expressing β-gal activity not only in the neurons of the inoculation site but also in the area projecting to the inoculation site, where this spread of area was regulated by an anti-HSV agent, ganciclovir. βH1 is originated from HSV-1 HF strain that is attenuated to mice, and expresses β-gal activity in the central nervous system (CNS), especially motor neurons in spinal cord without causing tissue destruction or inflammation. It would be a broad potential vector for gene therapy for familial amyotrophic lateral sclerosis and CNS diseases
|
