The Steinmetz Lab’s mission is to push to new frontiers in medicine and bio-nanotechnology through design, development and testing of materials and biologics derived from plant viruses. Our vision is the translation of promising candidates into clinical and commercial applications.
Next-generation nanotechnology depends upon the capacity to precisely alter size and shape of nanostructured features with temporal and spatial control. Nanoscale self-assembly is a technique that Nature masters with atomic precision; using this principle, we turned toward the study and application of plant viruses as an approach to generate highly structured nanoparticles with new functionalities. Viruses are playing a special role in nanotechnology, because they can function as prefabricated nanoparticles naturally evolved to deliver cargos and/or interact with cells and tissues in various environments. We have developed a library of plant virus-based nanoparticles and through structure-function studies we are beginning to understand how to tailor these nanomaterials appropriately for biomedical applications, precision farming, and engineered living materials.
Research is organized into several interconnected research thrusts:
- Vaccines and immunotherapies.
- Drug and gene delivery.
- Molecular imaging and theranostic approaches.
- Precision farming and agricultural nanotechnology.
- Living materials and plant cyborgs.
Please also see our Center for Nano-ImmunoEngineering (nanoie.ucsd.edu) and UC San Diego Materials Research and Engineering Center (mrsec.ucsd.edu).
Molecular farming and plant virus-based nanoparticles
Molecular farming: Microorganism and plants have long been utilized in the food and pharmaceutical industry to aid in fermentation processes or to produce pharmaceuticals. We are beginning to apply the concepts of plant molecular farming to engineer living materials systems; plant cyborgs that manufacture materials and/or are enhanced through synthetic parts.
Plant virus nanoparticles: Plant virus-based nanomaterials can be functionalized to impart new functionalities; the inner, outer and interface can be modified to carry medically relevant cargos. The precision and engineering design space is unmatched compared to conventional nanoparticle systems.
image credit: Soo Khim Chan, Ph.D.
Vaccines and Immunotherapy
Plant virus-based vaccines. Plant virus-like nanoparticles serve as potent adjuvants and epitope display platforms. We are developing plant VLP-based vaccines targeting cancer, cardiovascular disease and infectious diseases.
Plant VLP vaccine devices: Addressing the need for global immunization, we are developing implants and microneedle technology incorporating VLP vaccines.
Plant virus cancer immunotherapy. We demonstrated that nanoparticlesfrom a harmless plant virus, namely Cowpea mosaic virus (CPMV) stimulate apotent antitumor immune response in mouse models of melanoma, ovarian cancer,breast cancer, colon cancer and glioma. When thesenanoparticles are used as cancer immunotherapy and applied by intratumoralinjection, systemic and durable anti-tumor efficacy is achieved withimmunological memory to prevent metastatic disease and/or recurrence . Ongoing trials in companiondogs with melanoma indicate that the potent antitumor efficacy of the plantvirus-derived nanoparticles can be replicated in these animals . It isimportant to understand that the nanoparticle-stimulated immune-mediatedanti-tumor response is not limited totreatment of the identified, injectable tumor; our data indicate that the treatmentinduces a systemic, immune-mediated anti-tumor response against unrecognizedmetastases and protect patients from recurrence of the disease.
Drug delivery targeting human health
Drug and gene delivery: We are using plant virus-based drug delivery vehicles to target small molecule chemotherapies as well as nucleic acid therapeutics targeting cancer and cardiovascular disease.
Protein therapeutics: Capitalizing on the multivalent nucleoprotein assemblies formed by the filamentous plant viruses, we are developing display strategies for multivalent delivery of therapeutic proteins for cancer and thrombosis treatment.
Molecular imaging and theranostics
Plant virus based macromolecular contrast agents: Improving survival and quality of life, and reducing healthcare costs depends on better non-invasive imaging techniques with better prognostic value. Toward this goal, we are developing plant virus-based macromolecular contrast agents and have demonstrated optical, MRI, and photoacoustic imaging of cancer and cardiovascular disease in mouse models.
Theranostics: Toward tools that enable detection and treatment, we have developed a tobacco mosaic virus probe enabling detection and imaging of disease sites using optical, MRI, or photoacoustic imaging. Upon activation with near-infrared light, these probes also enable photothermal therapy.
Precision farming and agricultural nanotechnology
The first step towards a healthier society is to reduce exposure to toxic substances. There is an urgent need to change the way pesticides are used to protect our crops. We focus on developing more effective ways to treat plant endoparasitic nematodes feeding on crop roots.
Using Tobacco mild green mosaic virus (TMGMV) as a nanocarrier, we demonstrated anthelmintic drug delivery targeting nematodes. Data indicate superior soil mobility of TMGMV vs. contemporary nanomaterials; this opens the door for nanotechnology-assisted precision farming.
This is a new research direction... more information will follow shortly.
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