SITIS Topic Details |
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| Proposals Accepted: | |
| Program: | SBIR |
| Topic Number: | AF103-043 (AirForce) |
| Title: | Cellular Gene and Pathway Regulation | Research & Technical Areas: | Biomedical, Human Systems |
| Objective: | Develop novel materials and methods for the introduction of macromolecules to cells without the use of lipid or polymer carriers.
| Description: | Alternative methods are needed to introduce nucleic acids, peptides and proteins into various cell types. Current techniques include mechanical, electrical and chemical (i.e. use of as lipids and polymers) methods which have been developed to overcome the challenges of diminished cell entry, degradation by nucleases, and stimulation of an immune response. (1, 2) However, they often cause adverse reactions, off-target effects, and cellular toxicity. A robust and universal cellular transfection system is requested. These new techniques will enhance performance of systems and enable new strategies for genetic and pathway regulation. Introduction of nucleic acids will allow spatial temporal control over gene expression, modulation of cellular processes, and direct control over biological processes. These new methods would allow improvement in the health of deployed troops via minimally-invasive methods for medical treatment in the field, protection against biological and chemical threats by controlling gene expression and/or pathways. AFRL is interested in synthesizing, characterizing, and applying novel bio-inspired materials or biophysical methods for these purposes. Proposals are expected to be high risk/ high reward endeavors, and should combine aspects of materials science, nanotechnology, physics, chemistry, biology, and medicine for gene and pathway regulation.
| PHASE I: Design and demonstrate materials and methods for delivery of various macromolecules into prokaryotic and/or eukaryotic cells. Approaches that can deliver more than one type of macromolecule are preferred. These should include a DNA vector capable of expressing a fluorescent protein, siRNA, peptides, and proteins (such as antibodies, nanobodies, or enzymes). Delivery should be validated using two orthogonal approaches that include microscopy and a molecular biological technique. Research will include an analyses of delivery and toxicity of the proposed materials, as well as a comparative study with biophysical and/or electrical methods using commercially-available transfection agents, including lipids and polymers.
| PHASE II: Apply developed materials and/or methods for genetic and/or pathway regulation against 3 or more targets as determined by Phase I analyses and outcome. Approaches that are capable of delivering more than one class of macromolecule to both eukaryotic and prokaryotic cells will be given preference as will approaches that can target and modify function of more than one class of macromolecules. Delivery methods and materials should be modifiable to contain custom biomolecules including, nucleic acids, proteins, peptides and small molecules. Capabilities should be easily expanded to whole libraries of a specific class of molecule. Deliverables include materials which demonstrate ability to target cells of Air Force interest for improved human performance (including but not limited to immune, epithelial and neuronal cells).
| PHASE III | DUAL USE COMMERCIALIZATION: Military Application: Fundamental study will lead to a transition path to military application including new defense capabilities.
Commercial Application: Technology developed will have direct impact at improving and maintaining human health or transforming current research approaches.
| References: | 1. Pirollo, K. F.; Chang, E. H.Targeted delivery of small interfering RNA: approaching effective cancer therapies Cancer Res. 2008, 68, (5), 1247-1250. 2. Marques, J. T.; Williams, B. R. G. Activation of the mammalian immune system by siRNAs Nat. Biotechnol. 2005, 23, (11), 1399-1405. Keywords: cellular transfection, prokaryotic cells, eukaryotic cells, lipids, polymers, biomolecules |
| Keywords: | cellular transfection, prokaryotic cells, eukaryotic cells, lipids, polymers, biomolecules, non-invasive delivery of macromolecules, neuronal cells, immune cells, epithelial cells, |
Questions and Answers: |
Q: We have developed multifunctional nanoparticles that are magnetic, luminescent and concurrently provide high contrast MRI when injected in a mouse. We have shown that these Magnetic Nanophosphors (MNPs) can image cancerous tumor. The delivery MNPs with transferrin or anticancer drug using under external applied magnetic field is unequivocally demonstrated. We have also coated these particles with molecules such as PEG, thiol. Amine which will allow us to attach the MNPs to drugs for targeted drug delivery. MNPs have ability demonstrate cell-uptake using optical microscopy, MRI (in mice studies. All animal studies have been performed jointly with Albert Einstein College of Medicine, Bronx, NY. We hope to attach MNPs to small strands of RNA for cell uptake. Would our effort cover the objective of proposal? |
A: . . . response pending . . . |
As of midnight September 1, questions for solicitations SBIR 10.3 and STTR 10.B will no longer be accepted.
To read the solicitation for full proposal preparation and submission details click here. |