Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.
Reprod Domest Anim
; 52 Suppl 2: 354-358, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-27859771
ABSTRACT
The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cats
/
Dependovirus
/
Contraception
/
Gene Silencing
/
Genetic Vectors
/
Hypothalamus
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Reprod Domest Anim
Journal subject:
MEDICINA REPRODUTIVA
/
MEDICINA VETERINARIA
Year:
2017
Document type:
Article
Affiliation country: