Production of human factor IX in animals by genetically modified skin fibroblasts: potential therapy for hemophilia B.

نویسندگان

  • T D Palmer
  • A R Thompson
  • A D Miller
چکیده

Inherited diseases might be treated by introducing normal genes into a patient's somatic tissues to correct the genetic defects. In the case of hemophilia resulting from a missing clotting factor, the required gene could be introduced into any cell as long as active factor reached the circulation. We previously showed that retroviral vectors can efficiently transfer genes into normal skin fibroblasts and that the infected cells can produce high levels of a therapeutic product in vitro. In the current study, we examined the ability of skin fibroblasts to secrete active clotting factor after infection with different retroviral vectors encoding human clotting factor IX. Normal human fibroblasts infected with one vector secreted greater than 3 micrograms factor IX/10(6) cells/24 h. Of this protein, greater than 70% was structurally and functionally indistinguishable from human factor IX derived from normal plasma. This suggests that infected autologous fibroblasts might provide therapeutic levels of factor IX if transplanted into patients suffering from hemophilia B. By transplanting normal diploid fibroblasts infected with the factor IX vectors, we showed that human factor IX can be produced and is circulated at readily detectable levels in rats and mice.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Production of Human Factor IX in Animals by Genetically Modified Skin Fibroblasts : Potential Therapy for Hemophilia

Inherited diseases might be treated by introducing normal genes into a patient’s somatic tissues to correct the genetic defects. In the case of hemophilia resulting from a missing clotting factor. the required gene could be introduced into any cell as long as active factor reached the circulation. We previously showed that retroviral vectors can efficiently transfer genes into normal skin fibro...

متن کامل

Expression of Recombinant Coagulation Factor IX in Human Amniotic Membrane-derived Mesenchymal Stem Cells: A New Strategy to Gene Therapy of Hemophilia B

Background: Hemophilia B is an X-linked hereditary disorder of blood coagulation system which is caused by factor IX (FIX) deficiency. Factor IX is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. Replacement of factor IX with plasma-derived or recombinant factor IX is the conventional treatment for hemophilia B to raise the factor IX le...

متن کامل

Evaluation of the Relationship Between Factor IX Inhibitor in Hemophilia B Patients and Different Types of Therapy in the North-eastern Part of Iran

Background: Hemophilia B is a bleeding disorder with a recessive X-linked inheritance pattern, in which the infected individuals have low levels of factor IX in their plasma. Affected individuals may have bleeding episodes after trauma or spontaneously considering the plasma level of factor IX. In order to prevent these episodes and to control bleeding, they should use coagulation factor concen...

متن کامل

Molecular Characterization of the Factor IX Gene in 28 Iranian Hemophilia B Patients

Background: Heterogeneous mutations in the human coagulation factor IX gene lead to an X-linked recessive bleeding disorder known as hemophilia B. The disease is distributed worldwide with no ethnic or geographical priority. Materials and Methods: The aim of this study was to characterize the factor IX gene mutations in 28 unrelated Iranian hemophilia B patients. Polymerase chain reaction (PCR)...

متن کامل

[The skin as a vehicle for gene therapy: hemophilia B, an application model].

Artificial skin offers important advantages in gene therapy tor its biosafety and simple monitoring. An easy access of keratinocytes through small biopsies and their in vitro expansion enriched with epithelial stem cells, make them an ideal target for long-term therapeutic transgene expression. Corrective cutaneous gene therapy has been recently applied in clinical trials on dermatological gene...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Blood

دوره 73 2  شماره 

صفحات  -

تاریخ انتشار 1989