Gene introduction efficiency enhancer
A gene transfer efficiency enhancer of the present invention which contains a histone deacetylase inhibitor (especially compound (A)) as an active ingredient is capable of enhancing gene transfer efficiency in a gene transfer mediated by an adeno-associated virus vector while retaining the advantages of the adeno-associated virus vector.
1. A method for increasing transgene expression in a gene transfer mediated by an adeno-associated virus vector (AAV), comprising:
administering (a) an AAV comprising a transgene and (b) an effective dose of a histone deacetylase inhibitor to a human subject in need thereof, wherein:
the histone deacetylase inhibitor is a compound represented by formula (I):
or a salt or a derivative of the compound; and
the effective dose of a histone deacetylase inhibitor is an amount that results in increased expression of the transgene.
2. The method of claim 1 , wherein the histone deacetylase inhibitor is administered before administration of the adeno-associated virus vector.
3. The method of claim 1 , wherein the subject is an adult and the effective dose of the histone deacetylase inhibitor is 1 mg/m 2 to 50 mg/m 2 of a compound represented by formula (I):
or a salt or a derivative of the compound daily.
4. The method of claim 1 , wherein the AAV comprising a transgene and the histone deacetylase inhibitor are administered to tumor cells.
5. The method of claim 4 , wherein the method is performed for gene therapy, and the subject has cancer.
6. The method of claim 1 , wherein the method is performed for gene therapy and the subject has cancer; a neuromuscular disease; myotonic dystrophy; amyotrophic lateral sclerosis (ALS); heart failure; cardiomyopathy; diseases treated with protein supplementation therapy through expression of a secretory protein; chronic systemic diseases; arteriosclerosis; hypertension; heart failure; diabetes; hyperlipidemia; cerebral infarction; reperfusion injury after cerebral ischemia; Parkinson's disease; various neurodegenerative disease; mitochondrial encephalomyopathy; epilepsy; schizophrenia; or alcoholism.
7. A method for increasing the efficiency of a transduction mediated by an adeno-associated virus vector (AAV), comprising: administering (a) an AAV comprising a transgene and (b) an effective amount of a histone deacetylase inhibitor to human cells in need thereof, wherein:
the histone deacetylase inhibitor is a compound represented by formula (I):
or a salt or a derivative of the compound; and
the effective dose of a histone deacetylase inhibitor is an amount that results in increased transduction efficiency.
8. The method claim 7 , wherein the AAV comprising a transgene and the histone deacetylase inhibitor are administered to embryonic stem cells or hematopoietic stem cells.
9. The method as described in claim 7 , wherein the cells are tumor cells of a subject.
10. The method as described in claim 7 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
or a salt or a derivative of the compound.
11. The method according to claim 7 ,
wherein the cells are tumor cells of a subject, and
wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
or a salt or a derivative of the compound.
12. The method of claim 1 , wherein the histone deacetylase inhibitor is FK228.
13. The method of claim 7 , wherein the histone deacetylase inhibitor is FK228.
14. The method of claim 1 , wherein the derivative is obtained through acetylation of the compound or through reduction of the S—S bond of the compound.
15. The method of claim 7 , wherein the derivative is obtained through acetylation of the compound or through reduction of the S—S bond of the compound.