Repurposing biology

The Steinmetz Lab’s mission is to push to new frontiers in human and plant health 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.  Our approach is to redesign and repurpose naturally occurring nanoparticles derived from plant viruses.

Next-generation nanotechnology depends upon the capacity to precisely alter size and shape of nanostructured features with temporal and spatial control. In medicine and biology, phenomena happen at the nanoscale - hence nanoscale materials are particularly well suited to engage and interface with living systems. Plant viruses can be regarded as nature's nanomaterials - evolved to assemble with atomic precision to package and deliver cargo. While mammalian viruses have made headway in medicine, plant viruses offer advantages such as production in edible plants, high degree of stability (not requiring ultra-low freezers), and impeccable engineering design space. Through synthetic biology and chemical programming and assembly, plant viruses can be repurposed with new functionalities.  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 human health and plant health.

Research is organized into several interconnected research thrusts:

Human health 

  • Plant viral drug and gene delivery.
  • Vaccines and immunotherapies.

Precision farming

  • Agricultural nanotechnology to increase food security. 
  • Next-generation engineered living materials (ELMs) for diverse applications.

Please also see our Center for Nano-ImmunoEngineering, Center for Engineering in Cancer,  and UC San Diego Materials Research and Engineering Center.

Molecular farming of 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 (VLPs) serve as potent adjuvants and epitope display platforms. We are developing plant VLP-based vaccines targeting cancer, cardiovascular disease and infectious diseases.

Medical device technology incorporating plant virus biologics:  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.

Engineered Living Materials

This research is carried out under our UC San Diego Materials Research Science and Engineering Center (MRSEC).  We seek to develop methods to integrate engineered living matter, cells and plants, with polymeric materials. In doing so, we will create new composite materials that are responsive to diverse stimuli and capable of generating complex, genetically encoded material outputs. Our long-term research goals are to develop techniques that will enable the creation of materials at the living/non-living interface, with the potential for use in biosynthetic electronics, chemical threat decontamination, therapeutic synthesis/delivery, and soft robotics, among other applications. 

Find out more here: https://mrsec.ucsd.edu/living-materials

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