Plants produce a wide variety of valuable bioactive metabolites, but these are commonly present in low concentrations in the wild-type plant. This makes the separation and purification of these compounds complicated and expensive. The applicant company, Naprogenix Inc, has developed a technology for increasing the yields of specific bioactive metabolites in mutant plant cell cultures, which promises to lessen this problem. However, the value of this, or any other approach using genetically-modified plant cells, is limited by the necessity of the wasteful destruction of the plant cells in order to extract the required products. The process would be more efficient if products could be harvested from cells in continuous culture. Nanoparticles are taken up by cells by endocytosis, and subsequently exocytosed. They can also be engineered to adsorb specific chemicals. This suggests that specifically-engineered (functionalized and magnetized) nanoparticles could be used to repeatedly "harvest" specific metabolites from living plant cell cultures. One of the company's major projects is designed to generate novel flavonoids in goldenrod hairy root cultures. The applicants have shown that functionalized silica nanoparticles adsorb similar flavonoids and that they are taken up and removed from these plant cell cultures without compromising the viability of the cultures. The objective is now to engineer optimally-functionalized magnetized silica nanoparticles (by collaborators at the University of Kentucky) to harvest specific flavonoids from these hairy roots.
The specific aims of phase I are to show that (a) exposure to these nanoparticles translocate flavonoids from the intracellular compartment of hairy roots to the extracellular medium (b) these extracellular magnetized nanoparticles can be concentrated in a magnetic field (c) significant amounts of flavonoids can be eluted and collected from these nanoparticles following their passage through plant cells. If this is successful, then, in phase II, the applicants will design ad test nanoparticles for harvesting other bioactive metabolites from optimized plant cell cultures. These will include very high value chemotherapeutic agents, such as the taxoids and vinca alkaloids. If successful this approach should make a major impact on the use of plant cell cultures for the production and isolation of high value natural products. The nanoparticles, and the harvesting technologies as applied to plant cells, are patentable, and have major commercial implications for the applicant company and the University.

Public Health Relevance

Many valuable plant compounds can be produced in tissue culture, but their isolation requires destruction of the plant tissue before chemically separating the required compounds from others. This project aims to develop magnetized nanoparticle devices that can be used to remove specific types of compounds from living plant tissue. This is predicted to greatly increase the efficiency of producing medicines or nutrients in plant tissue culture. These devices will also increase the commercial value of the proprietary biotechnology used by the applicant company, which is designed to optimize plant cell cultures for their ability to produce specific natural products.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41AT008312-01
Application #
8712853
Study Section
Special Emphasis Panel (ZRG1-IMST-M (13))
Program Officer
Williamson, John S
Project Start
2014-06-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$189,844
Indirect Cost
Name
Naprogenix, Inc
Department
Type
DUNS #
196165877
City
Lexington
State
KY
Country
United States
Zip Code
40546