Gene therapy for inherited hyperbilirubinemias

Namita Roy-Chowdhury, Ajit Kadakol, Baljit S. Sappal, Narsing R. Thummala, Siddhartha S. Ghosh, Sung W. Lee, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalJournal of Perinatology
Volume21
Issue numberSUPPL. 1
StatePublished - 2001

Fingerprint

Genetic Therapy
Gunn Rats
bilirubin glucuronoside glucuronosyltransferase
Crigler-Najjar Syndrome
Kernicterus
Animal Disease Models
Simian virus 40
Viral Genes
Cell- and Tissue-Based Therapy
Site-Directed Mutagenesis
Bilirubin
Adenoviridae
Liver Transplantation
Hepatocytes
Transplantation
Liver
Genes
Therapeutics

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Pediatrics, Perinatology, and Child Health

Cite this

Roy-Chowdhury, N., Kadakol, A., Sappal, B. S., Thummala, N. R., Ghosh, S. S., Lee, S. W., & Roy-Chowdhury, J. (2001). Gene therapy for inherited hyperbilirubinemias. Journal of Perinatology, 21(SUPPL. 1).

Gene therapy for inherited hyperbilirubinemias. / Roy-Chowdhury, Namita; Kadakol, Ajit; Sappal, Baljit S.; Thummala, Narsing R.; Ghosh, Siddhartha S.; Lee, Sung W.; Roy-Chowdhury, Jayanta.

In: Journal of Perinatology, Vol. 21, No. SUPPL. 1, 2001.

Research output: Contribution to journalArticle

Roy-Chowdhury, N, Kadakol, A, Sappal, BS, Thummala, NR, Ghosh, SS, Lee, SW & Roy-Chowdhury, J 2001, 'Gene therapy for inherited hyperbilirubinemias', Journal of Perinatology, vol. 21, no. SUPPL. 1.
Roy-Chowdhury N, Kadakol A, Sappal BS, Thummala NR, Ghosh SS, Lee SW et al. Gene therapy for inherited hyperbilirubinemias. Journal of Perinatology. 2001;21(SUPPL. 1).
Roy-Chowdhury, Namita ; Kadakol, Ajit ; Sappal, Baljit S. ; Thummala, Narsing R. ; Ghosh, Siddhartha S. ; Lee, Sung W. ; Roy-Chowdhury, Jayanta. / Gene therapy for inherited hyperbilirubinemias. In: Journal of Perinatology. 2001 ; Vol. 21, No. SUPPL. 1.
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