Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Mol Ther ; 19(2): 326-34, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21119620

RESUMEN

AAV2-sFLT01 is a vector that expresses a modified soluble Flt1 receptor designed to neutralize the proangiogenic activities of vascular endothelial growth factor (VEGF) for treatment of age-related macular degeneration (AMD) via an intravitreal injection. Owing to minimal data available for the intravitreal route of administration for adeno-associated virus (AAV), we initiated a 12-month safety study of AAV2-sFLT01 administered intravitreally at doses of 2.4 × 10(9) vector genomes (vg) and 2.4 × 10(10) vg to cynomolgus monkeys. Expression of sFlt01 protein peaked at ~1-month postadministration and remained relatively constant for the remainder of the study. Electroretinograms, fluorescein angiograms, and tonometry were assessed every 3 months, with no test article-related findings observed in any group. Indirect ophthalmoscopy and slit lamp exams performed monthly revealed a mild to moderate but self-resolving vitreal inflammation in the high-dose group only, which follow-up studies suggest was directed against the AAV2 capsid. Histological evaluation revealed no structural changes in any part of the eye and occasional inflammatory cells in the trabecular meshwork, vitreous and retina in the high-dose group. Biodistribution analysis in rats and monkeys found only trace amounts of vector outside the injected eye. In summary, these studies found AAV2-sFLT01 to be well-tolerated, localized, and capable of long-term expression.


Asunto(s)
Dependovirus/genética , Terapia Genética/métodos , Vectores Genéticos/genética , Degeneración Macular/terapia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Macaca fascicularis , Degeneración Macular/genética , Ratones , Reacción en Cadena de la Polimerasa , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética
2.
J Androl ; 26(2): 272-80, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15713834

RESUMEN

Recent work from our laboratory provided evidence for the existence of a nuclease in hamster spermatozoa. This endogenous nuclease cleaves sperm chromatin at the bases of DNA loop domains into large fragments with an average size of roughly 50 kb. Here, we demonstrate that this sperm nuclease is present in the sperm nucleus and that it is activated by the presence of both calcium and magnesium much more efficiently than with either ion alone, resulting in DNA degradation in 30 minutes. We also show that similar nucleases are present in mouse and human spermatozoa. The human nuclease can be activated by freeze-thawing spermatozoa in noncryoprotective media. The activity of the sperm nuclease in all 3 species resembles that of a group of somatic cell DNAses that also require both calcium and magnesium and that digest the chromatin into loop-sized fragments during apoptosis.


Asunto(s)
Núcleo Celular/enzimología , Desoxirribonucleasas/metabolismo , Espermatozoides/enzimología , Animales , Cricetinae , Humanos , Infertilidad Masculina/enzimología , Masculino , Ratones , Especificidad por Sustrato
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA