National Center for Complementary and Alternative Medicine (NCCAM)

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Natural Products Methods Development

Project Concept Review

Council Date: February 1, 2013

Program Officer: John Williamson and Craig Hopp

Background

Natural products are essential sources of medicines. The World Health Organization estimates that ~80% of the world’s population relies on traditional medicines made from natural products. The modern pharmaceutical industry is also dependent on plant-based medicines, with as much as 50% of all drugs based on natural products or derived from a natural product origin. Clearly, plants and other natural products offer excellent sources of health-promoting medicines. Thus it is extremely important that we enhance our capacity to further examine these traditional modalities and achieve a solid scientific understanding of their potential health benefits.

Nonetheless, substantial problems exist in identifying and understanding natural products and their bioactivity. While the potential for natural products in health and wellbeing is clear, the challenges that hamper the full utilization of these resources are many, with the greatest hurdle simply being the enormous amount of time and effort required for structure identification and characterization of the mechanisms by which natural products exert their pharmacological activity. Improvements in collection, bioassay, isolation, purification, de-replication, yield, and supply of natural products are possible. While advances have been made to help overcome these hurdles, there exist many new untapped technological resources that may improve natural products research methodologies.

Purpose of Proposed Initiative

The proposed initiative will utilize NCCAM’s Small Business Innovation Research (SBIR) Grant set-aside program to solicit grants directed at stimulating the development of new and improved technologies for natural products research. The purpose of NCCAM’s Small Business Innovation Research (SBIR) Grant program is to stimulate technological innovation in the private sector, strengthen the role of small business in meeting Federal research or research and development needs, and improve the return on investment from Federally funded research for economic and social benefits to the Nation. In addition, a newly mandated expansion of the SBIR Grant program offers NCCAM the ability to further enhance efforts to expand the natural products portfolio.

Natural products offer a diverse reservoir of biologically active components. The single chemical entities, as well as their mixtures in natural product extracts, have a long history of use as drugs, drug precursors, and/or complementary health adjuvants. However, methodologies for the identification of bioactive natural products and their mechanism(s) of pharmacological action are often inadequate or too time-consuming to be compatible with modern screening platforms. We believe that many existing biotechnologies could be adapted to improve natural products research. Innovative methods might utilize genomics, bio-products engineering, bioinformatics, synthetic and molecular biology, or nanotechnology. The purpose of this proposed initiative is to improve upon the currently available natural products methodologies, thereby increasing the efficiency of research in this field.

Objectives

With this SBIR initiative, NCCAM is proposing to focus on five areas that could significantly improve the progress in natural products research:

  • Technologies aimed at improving field applications for characterizing natural product sources/species and their diverse bioactive constituents (examples—DNA barcoding, gene chips, activity-based profiling, biosensors, spectrometric equipment and techniques, etc.),
  • Technologies aimed at the rapid de-replication and removal of nuisance compounds in the crude extracts of natural products (examples—innovative chromatographic technologies, resins, catch and release-type systems, etc.),
  • Technologies aimed at the development of highly sensitive phenotypic/high content bioassays including capacity to identify potential synergistic mechanisms (examples—image-based cellular assays, multiple-endpoint analysis based on phenotypic changes, bioengineering chemically sensitive strains, etc.),
  • Technologies aimed at the creation and exploitation of model systems for the expression of natural product constituents in high product yielding hosts (broad spectrum heterologous or homologous expression hosts, stimulation of biosynthetic pathways, mutation, etc.), and
  • Technologies aimed at predicting and/or quantifying risks of natural product–drug interactions (examples—designed in vitro interaction assays or kits, in silico technologies, etc.).