TY - JOUR
T1 - Gene therapy for inherited hyperbilirubinemias
AU - Roy-Chowdhury, Namita
AU - Kadakol, Ajit
AU - Sappal, Baljit S.
AU - Thummala, Narsing R.
AU - Ghosh, Siddhartha S.
AU - Lee, Sung W.
AU - Roy-Chowdhury, Jayanta
N1 - Funding Information:
This work was supported, in part, by the following NIH grants: DK 39137 ( to N. R. C. ), DK 46057 (to J. R. C.), Liver Research Core Center (P30-DK 41296), General Clinical Research Center (1M01 RR12248-04).
PY - 2001/12/1
Y1 - 2001/12/1
N2 - Crigler-Najjar syndrome type 1 (CN-1) is a potentially lethal condition, and is the only inherited disorder of bilirubin metabolism that needs treatment beyond the neonatal period. Currently, orthotopic liver transplantation is the only available cure for CN-1. Because the liver architecture is not disturbed in CN-1 and partial correction of bilirubin-UDP-glucuronosyltransferase (UGT1A1) activity is expected to be sufficient for protection against kernicterus, cell and gene therapies are being developed using the Gunn rat as an animal model of the disease. Ex vivo gene therapy based on the transplantation of genetically manipulated hepatocytes and in vivo gene transfer using recombinant adenovirus and Simian virus 40 (SV40)–based vectors have yielded significant success. The novel strategy of in vivo site-directed mutagenesis has also resulted in modest, but significant, correction of the genetic abnormality. Newer viral and nonviral gene delivery methods are being explored and have been discussed in brief. In summary, effective gene therapy methods have been validated in Gunn rats. Despite considerable remaining hurdles, gene therapy for CN-1 could become a clinical reality by the turn of this decade.
AB - Crigler-Najjar syndrome type 1 (CN-1) is a potentially lethal condition, and is the only inherited disorder of bilirubin metabolism that needs treatment beyond the neonatal period. Currently, orthotopic liver transplantation is the only available cure for CN-1. Because the liver architecture is not disturbed in CN-1 and partial correction of bilirubin-UDP-glucuronosyltransferase (UGT1A1) activity is expected to be sufficient for protection against kernicterus, cell and gene therapies are being developed using the Gunn rat as an animal model of the disease. Ex vivo gene therapy based on the transplantation of genetically manipulated hepatocytes and in vivo gene transfer using recombinant adenovirus and Simian virus 40 (SV40)–based vectors have yielded significant success. The novel strategy of in vivo site-directed mutagenesis has also resulted in modest, but significant, correction of the genetic abnormality. Newer viral and nonviral gene delivery methods are being explored and have been discussed in brief. In summary, effective gene therapy methods have been validated in Gunn rats. Despite considerable remaining hurdles, gene therapy for CN-1 could become a clinical reality by the turn of this decade.
UR - http://www.scopus.com/inward/record.url?scp=0035684050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035684050&partnerID=8YFLogxK
U2 - 10.1038/sj.jp.7210646
DO - 10.1038/sj.jp.7210646
M3 - Article
C2 - 11803431
AN - SCOPUS:0035684050
SN - 0743-8346
VL - 21
SP - S114-S118
JO - Journal of Perinatology
JF - Journal of Perinatology
ER -