(13) Smart Biomaterials - Theranostics 13-EB-101*Theranostics: Combined delivery of diagnostic and therapeutic agents. Multimeric polyspecific protein therapeutics are difficult to design and produce. The ability to link binding, effector, and imaging components together in a single molecule would be a significant advantage. We propose to develop unnatural amino acid- oligonucleotide technology (UAA-oligo) in order to precisely control formation of modular therapeutics and diagnostics. An unnatural amino acid engineered in a single position will allow site-specific coupling of an oligonucleotide. The oligonucleotide can then be hybridized to its complement which is conjugated to a second modular protein. The base-pairing rules of DNA will allow higher order heterodimers, trimers, tetramers, and other multimers to be produced. This strategy will allow diagnostic and therapeutic modules to be coupled in a single molecule to produce a """"""""Theranostic"""""""".

Public Health Relevance

The ability to create modular protein therapeutics, such that novel binding, effector, and diagnostic proteins can be combined in a single """"""""theranostic"""""""" has considerable importance in medicine. Specifically, this proposal aims to create the platform for discovery of such molecules as well as for their facile construction. We will use oligonucleotides and unnatural amino acids to site specifically link two or more proteins together through the complementary base pairing of nucleic acids. Molecules that we create could simultaneously detect, bind, and kill tumor cells through imaging, binding, and toxin modules. This """"""""lego"""""""" block assembly process will allow a vast array of combinatorial protein theranostic modules to be created and evaluated against a myriad of diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
NIH Challenge Grants and Partnerships Program (RC1)
Project #
5RC1EB010745-02
Application #
7936183
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (58))
Program Officer
Zullo, Steven J
Project Start
2009-09-30
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$499,999
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Kazane, Stephanie A; Axup, Jun Y; Kim, Chan Hyuk et al. (2013) Self-assembled antibody multimers through peptide nucleic acid conjugation. J Am Chem Soc 135:340-6
Hutchins, Benjamin M; Kazane, Stephanie A; Staflin, Karin et al. (2011) Site-specific coupling and sterically controlled formation of multimeric antibody fab fragments with unnatural amino acids. J Mol Biol 406:595-603
Hutchins, Benjamin M; Kazane, Stephanie A; Staflin, Karin et al. (2011) Selective formation of covalent protein heterodimers with an unnatural amino acid. Chem Biol 18:299-303