Our goal is to establish basic science foundations and engineering principles for the broad applications of theranostic (therapeutic+diagnostic) nano-objects, defined as compact autonomous molecular devices capable of analyzing multiple biomarkers before signaling that there are pathological events or before taking corrective actions. Our effort will center on methods to control behavior of dynamic neggs (nano-eggs), made of deoxyribonucleic acids, and comprising sensors, imaging and/or therapeutic moieties, and molecular computing functions. Neggs can open (be unlocked) or close (be locked) on cue, and this cue can be integrated information on the presence or absence of one or more biomarkers. In order to showcase the transformative potential of theranostic nano-objects, we will map increasingly complex engineered behaviors of neggs to proof-of-concepts for therapeutic applications for which no other existing technologies are satisfactory. For example, we will: (i) open a negg if an analyte raises above (e.g., glucose) or drops below (e.g., vasopressin) its normal concentration; (ii) mark for elimination/imaging narrow subpopulations of cells based on multiple surface markers, while protecting cells that differ in a single marker (e.g., on lymphocytes); and (iii) demonstrate amplification of MRI contrast agents on a targeted cell type (exemplified on b-cells). 1

Public Health Relevance

Theranostic (therapeutic+diagnostic) nano-objects are autonomous nanoscopic devices capable of analyzing in vivo multiple biomarkers before signaling the presence of pathological events (imaging/diagnostics) or before taking corrective actions when needed (therapeutics). They can autonomously control levels of glucose in diabetes, prevent irreversible shock in an intensive care patient, or selectively eliminate very narrow subpopulations of cells in a cancer patient.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM104960-04
Application #
8917274
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Lewis, Catherine D
Project Start
2012-09-27
Project End
2017-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
4
Fiscal Year
2015
Total Cost
$1,042,320
Indirect Cost
$226,430
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Jiang, Dawei; Ge, Zhilei; Im, Hyung-Jun et al. (2018) DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury. Nat Biomed Eng 2:865-877
Nakatsuka, Nako; Yang, Kyung-Ae; Abendroth, John M et al. (2018) Aptamer-field-effect transistors overcome Debye length limitations for small-molecule sensing. Science 362:319-324
Olsen, Timothy R; Tapia-Alveal, Claudia; Yang, Kyung-Ae et al. (2017) INTEGRATED MICROFLUIDIC SELEX USING FREE SOLUTION ELECTROKINETICS. J Electrochem Soc 164:B3122-B3129
Olsen, Timothy; Zhu, Jing; Kim, Jinho et al. (2017) An Integrated Microfluidic SELEX Approach Using Combined Electrokinetic and Hydrodynamic Manipulation. SLAS Technol 22:63-72
Simmons, Chad R; Zhang, Fei; MacCulloch, Tara et al. (2017) Tuning the Cavity Size and Chirality of Self-Assembling 3D DNA Crystals. J Am Chem Soc 139:11254-11260
Liu, Minghui; Fu, Jinglin; Qi, Xiaodong et al. (2016) A Three-Enzyme Pathway with an Optimised Geometric Arrangement to Facilitate Substrate Transfer. Chembiochem 17:1097-101
Zhang, Fei; Jiang, Shuoxing; Li, Wei et al. (2016) Self-Assembly of Complex DNA Tessellations by Using Low-Symmetry Multi-arm DNA Tiles. Angew Chem Int Ed Engl 55:8860-3
Kim, Jinho; Olsen, Timothy R; Zhu, Jing et al. (2016) Integrated Microfluidic Isolation of Aptamers Using Electrophoretic Oligonucleotide Manipulation. Sci Rep 6:26139
Yang, Kyung-Ae; Pei, Renjun; Stojanovic, Milan N (2016) In vitro selection and amplification protocols for isolation of aptameric sensors for small molecules. Methods 106:58-65
Zhao, Zhao; Fu, Jinglin; Dhakal, Soma et al. (2016) Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. Nat Commun 7:10619

Showing the most recent 10 out of 14 publications