DNA Molecule Encoding the B3 Adrenegic Receptor

Case ID:
92-249

This technology describes the correct protein sequence of the β3 receptor to aid in the development of adult-onset diabetes drugs.

 

Background & Unmet Need:

The β3 receptor is currently being developed as a therapeutic target for human obesity and adult onset diabetes mellitus by several pharmaceutical companies.  In order to develop selective agents (drugs that stimulate β3 receptors, but not other receptor subtypes), it is imperative to have the correct protein sequence.  Our researchers have discovered that the human β3 receptor is larger than previously believed.  Many mammalian genes are organized into units that encode instructions for the cell, called exons, and non-coding sequences, called introns.  The human β3 receptor gene was believed to contain only one exon and no introns.  We have discovered that the human β3 receptor gene contains an additional exon that encodes six amino acids.  To date, only the gene for the human β3 receptor has been cloned.  On the basis of the gene sequence, it was incorrectly deduced that the protein-coding block for the protein ends at amino acid 402.  Our researchers discovered that the sequence containing the deduced stop codon is in fact a donor splice site and that the coding block for the protein continues.

 

Technology Description:

Our researchers have discovered that the human β3 receptor gene contains one or more introns.  They have cloned the human β3 receptor cDNA that encodes this novel amino acid sequence.  It is unclear whether the additional sequence alters the pharmacological characteristics of the receptor; however, drug companies will need to be sure and to develop their compounds using the correct sequence.  Our researchers have evidence that the cells expressing gene constructs that are based upon the original sequence make truncated receptors as well as unanticipated fusion proteins.  There is an immediate opportunity to provide “repair kits” for these constructs.

 

Commercial Applications:

  • Screening test for pharmaceutical or agricultural compounds
  • Screening test for gene-modulating compounds to improve adult-onset diabetes

 

Stage of Development:

Preclinical

 

Competitive Advantages:

  • Correct sequence allows for more effective development of drug compounds

 

Intellectual Property Status:

U.S. Patent #5,364,772.

 

Related Publications or Citations of Work:

Granneman JG., Lahners, KN., and Chaudhry A. (1991) Molecular cloning and expression of the Rat β3-Adrenergic receptor. Mol. Pharmacol. 40:895-9.

 
 
Patent Information:
For Information, Contact:
Joan Dunbar
Associate Vice President for Technology Commercialization
Wayne State University
(313) 577-5542
jcdunbar@med.wayne.edu
Inventors:
James Granneman
Kristine Lahners
Donald Rao
Keywords:
Diabetes
Disease
DNA
Drug Target
Obesity
Therapeutics