Neurogenin 3 promoter

Abstract

The present invention features polypeptides having activity of human neurogenin3 (hNgn3), and nucleic acid encoding such polypeptide. The invention also features use of islet transcription factors such as hNgn3 to facilitate production of pancreatic islet cells from progenitor cells, and to facilitate insulin delivery by production of islet cells so produced.

Description

[0001] This application is 1) a continuation-in-part of PCT application serial no. PCT / US02 / 11166, filed Mar. 20, 2002 designating the United States and published in English, and 2) a continuation-in-part of U.S. application Ser. No. 09 / 817, 360, filed Mar. 20, 2001, which application is a continuation-in-part of U.S. application Ser. No. 09 / 535,145, filed Mar. 24, 2000, which application is entitled to the benefit of U.S. Provisional Application Serial No. 60 / 128,180, filed Apr. 6, 1999. The disclosures of each of these applications are incorporated herein by reference in their entireties.[0002] The invention relates generally to the field of delivery of insulin to a subject by production of islet cells, particularly insulin producing beta cells, and to islet transcription factors useful in such delivery (e.g., human neurogenin3).[0003] Diabetes mellitus is the third leading cause of death in the U.S. and the leading cause of blindness, renal failure, and amputation. Diabetes is al...

AI Technical Summary

Benefits of technology

0111] It should be noted that the invention contemplates the hNgn3 polypeptides and variants thereof described herein, as well as nucleic acids encoding such variants. When provided with guidance as to the amino acid sequence of a polypeptide and particularly wher

Problems solved by technology

Diabetes is also a major cause of premature heart attacks and stroke and accounts for 15% of U.S. health care costs.

Unfortunately, about one-half of the people in the U.S. affected by Type 2 diabetes are unaware that they have the disease.

Clinical symptoms associated with Type 2 diabetes may not become obvious until late in the disease, and the early signs are often misdiagnosed, causing a delay in treatment and increased complications.

Unfortunately, islet cell regeneration does not appear to occur when the islet cells alone are damaged, such as in type 1 diabetes.

Second, as discussed above, insulin production is impaired in individuals with diabetes.

In type 1 diabetes the impairment is caused by the destruction of the .beta.-cells, while in type 2 diabetes, insulin production is intact, but inadequate.

To date this has been largely unsuccessful.

A negative regulator of the islet transcription factor pathway is one that inhibits expression of a particular islet transcription factor or its downstream effectors, and thus negatively affects the induction of the islet cell phenotype.

A negative regulator of the Ngn3 pathway is one that inhibits expression of Ngn3 or its upstream or downstream effectors (e.g., HES1), and thus negatively affects the induction of the islet cell phenotype.

A negative regulator of the NeuroD1 pathway is one that inhibits expression of NeuroD1 or its upstream or downstream positive effectors, and thus negatively affects the induction of the islet cell phenotype.

A negative regulator of the Mash1 pathway is one that inhibits expression of Mash1 or its upstream or downstream effectors, and thus negatively affects the induction of the islet cell phenotype.

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