Photo of Novalia Pishesha

Biotechnology & medicine

Novalia Pishesha

Nanobodies that can be used as a therapeutic agent for a variety of human autoimmune diseases.

Year Honored

Harvard University

Asia Pacific

Hails From
Asia Pacific

A recent review of published evidence finds that global rates of autoimmune diseases have increased considerably over the past 30 years, particularly in industrialized nations. Estimates from the National Institutes of Health (NIH) suggest that there are more than 23 million people in the United States living with autoimmune diseases. No cures have yet been discovered for autoimmune diseases, although treatments that manage or alleviate the symptoms are available for many of them.

New treatments that prevent and alleviate autoimmune diseases may come from using engineered red blood cells to carry disease-specific proteins that retrain the immune system. During her PhD, Nova has developed and showed that such an approach works in mice with multiple sclerosis and type 1 diabetes. Even though engineered RBCs can successfully tackle autoimmune diseases, cellular biologics are expensive and won’t be affordable and scalable in developing countries. Hence, Nova redirected her attention to engineering alpaca-derived single domain antibody fragments (nanobodies/VHHs) as a completely proteinaceous platform that is highly scalable, cheap/fast to produce, and can be shipped at room temperature or even lyophilized. Nova has developed an engineered version of an alpaca nanobody/VHH that binds to an MHC Class 2 protein specifically expressed on antigen-presenting cells. She showed that a chimera of this VHH with any of several immunogenic peptides, when injected into an appropriate mouse strain, led to immune tolerance to the parent protein. In particular, injecting into mice a chimera of this VHH with a myelin oligodendrocyte glycoprotein (MOG) peptide, prior to the induction of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, completely prevented the development of clinical symptoms. More remarkably, transfusion of this VHH-MOG conjugate, together with a conjugate of the same VHH with a glucocorticoid, into mice where diseases had already been induced, halted, and even reversed to a significant degree the EAE symptoms. Just a single dose of these engineered nanobodies has shown robust in-vivo efficacy for treating preclinical mouse models of not only multiple sclerosis but also type I diabetes and rheumatoid arthritis. This treatment works for a lifetime and without compromising the capacity of the immune system to fight pathogens.

This technology has the promise of being applicable as a therapeutic for several human autoimmune diseases, including multiples clerosis and type I diabetes, as well as preventing the induction of immune responses to injection of foreign proteins or virus gene therapy vectors. She has furthered built on the modularity of this nanobody platform to generate COVID-19 and malaria vaccine candidates.