Virulence factor of Mycobacterium tuberculosis as a cellular delivery agent
- *Abstract
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Dr. Lee Riley, formerly of Cornell but now at the University of California at Berkeley (UCB), identified and cloned a key gene by means of which Mycobacterium tuberculosis (Mtb) gains access to macrophages and other cell types. Dr. Riley has been working to develop compositions and methods to harness this virulence factor for the delivery of drugs or other agents into such cells.
Within the gene responsible, dubbed mycobacterium cell entry (mce1), Dr. Rileys group identified a small segment encoding a 22 amino acid peptide required for this cellular transduction. Dr. Riley's group has used the transduction domain to introduce protein-coated latex microspheres and whole E. coli into HeLa cells. The transduction appears to require the interaction of the invaded cells actin cytoskeleton, Rho-family GTPases, and microtubules.
The enhanced cellular uptake of products carrying this domain has utility in research and in therapeutic applications. Therapeutically it can reduce drug dosages, thus reducing toxicity and cost. drug dosages, thus reducing toxicity and cost. The invention can also be utilized in conjunction with gene therapy regimens. In particular, the ability of the peptides to augment uptake into macrophages provides an opportunity to deliver genes specifically to such cells.
Cornell's issued patents claim DNA sequences, expressed proteins and peptides, expression systems, and methods of use, including drug delivery.
For information about related inventions Dr. Riley has developed at UCB, please contact
Javed Afzal, Ph.D., Licensing Officer, Life Sciences, 510-643-7201, jafzal@uclink.berkeley.edu
- *Licensing
- Dan-Oscar Antsonda429@cornell.edu212-746-1297
- 其他
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Arruda S et al. (1993) Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells. Science. 261(5127):1454-7.
Casali N et al (2002) Invasion activity of a Mycobacterium tuberculosis peptide presented by the Escherichia coli AIDA autotransporter. Infect Immun. 70(12):6846-52.
Chitale S et al. (2001) Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry. Cellular Microbiology 3(4), 247-254
Lu S et al (2006) A cell penetrating peptide derived from mammalian cell uptake protein of Mycobactium tuberculosis Anal Biochem 353:7-14.
- 国家/地区
- 美国
