PMID: 7544665Jun 1, 1995Paper

Circulating human factor IX produced in keratin-promoter transgenic mice: a feasibility study for gene therapy of haemophilia B

Human Molecular Genetics
M Y AlexanderR J Akhurst

Abstract

It has previously been suggested that keratinocytes might provide a suitable target cell for delivery of factor IX to the systemic circulation for gene therapy of haemophilia B. Here, an investigation of the use of cellular gene promoters specific for keratinocytes was undertaken to examine whether factor IX could be passed from the epidermis to the systemic circulation. Utilizing two bovine cytokeratin gene promoters, BKIII and BKVI, three lines of transgenic mice were generated with targeted expression of human factor IX in the epidermis. All three transgenic mouse lines secreted epidermally derived human factor IX into the blood system. Most effective factor IX expression (46 ng/ml steady-state levels of circulating human factor IX) was obtained utilizing the BKVI gene promoter, the human homologue of K10, which is expressed exclusively in differentiated keratinocytes, localized distal to the basement membrane. This report demonstrates, for the first time, that human factor IX can be efficiently synthesized and secreted from keratinocytes in situ, and can cross the epidermal basement membrane to reach the systemic circulation. The transgenic mouse model will provide a good in vivo system with which to optimize the efficiency...Continue Reading

Citations

Jun 14, 2002·Academic Radiology·Peter VaradyGregory A Helm
Jun 3, 1999·Proceedings of the Association of American Physicians·L B Taichman
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·M B MathorM De Luca
Nov 21, 2000·Human Gene Therapy·T CaoD R Roop
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·X WangE Fuchs
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·K Takahashi, P A Coulombe
Jun 4, 2004·Expert Opinion on Biological Therapy·Steven S Fakharzadeh
Sep 14, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·U R Hengge, A Mirmohammadsadegh
Feb 13, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·D WolfeJ C Glorioso
Jun 1, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bharat G BajajStelios T Andreadis
Jun 28, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·F LarcherJ L Jorcano
Mar 20, 1999·The Journal of Investigative Dermatology·W H YuR J Debs
Aug 1, 1997·The Journal of Investigative Dermatology·S M Page, G G Brownlee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.