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Northeastern University Researcher Studies Novel Oral Gene Therapy Method to Treat Inflammatory Bowel Disease

$1.34 Million Grant to Fund Research on Non-Viral DNA Delivery System

The treatment of inflammatory bowel disease (IBD), which afflicts as many as 10 individuals in 100,000 in the United States, is currently restricted to drugs being administered frequently through injections with short-term effects and toxic side effects. Oral gene therapy is the most promising non-invasive treatment with long-lasting effects and Northeastern University professor Mansoor Amiji and his interdisciplinary team have just been awarded $1.34 million by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) to evaluate the effectiveness of a novel DNA delivery system, called Nanoparticles-in-Microsphere Oral System or NiMOS.

“This will be the first study to examine the role of safe and effective non-viral gene delivery system for treatment of IBD upon oral administration,” said Amiji, Professor and Associate Department Chairman of the Pharmaceutical Sciences Department in Northeastern’s Bouve College of Health Sciences.

NiMOS is specifically designed as an intestinal mucosal DNA delivery system for oral gene therapy. Plasmid DNA encoding for a therapeutic protein is encapsulated in the nanoparticles, which are further protected by a polymeric microsphere matrix. When administered orally, the outer polymeric microsphere shell degrades in the presence of intestinal enzymes to release the nanoparticles, which are internalized by the cells of small and large intestine. The nanoparticles protect DNA during cellular transport and afford efficient transfection of the encoded protein therapeutic. Preliminary studies to confirm the potential of this technology for oral gene therapy was performed by Dr. Mayank Bhavsar, a recent graduate from Amiji’s lab.

Current research suggests that IBD results from alteration in the delicate physiological balance between the local expressions of pro- (e.g.: tumor necrosis factor-alpha or TNF-alpha) and anti-inflammatory (e.g.: interleukin-10 or IL-10) protein molecules, called cytokines, in the gastrointestinal tract. As part of evaluating NiMOS as a treatment method, Amiji and his team will study the effectiveness of two strategies: increasing the level of production of anti-inflammatory cytokines and decreasing the level of pro-inflammatory cytokines by getting them to bind with decoy receptors.

“Based on the preliminary studies, we anticipate that orally administered NiMOS formulations will provide target-specific delivery and transfection of anti-inflammatory cytokines and soluble receptors in the small and large intestines for treatment of this disease,” added Amiji, who is also the Co-Director of Nanomedicine Education and Research Consortium (NERC) at Northeastern University.

By encapsulating the plasmid DNA encoding for either IL-10 or TNF-alpha soluble receptor, the researchers can protect the DNA molecules from being degraded by the pH- and enzyme-mediated conditions in the gastrointestinal tract. This method has the promise of non-invasive oral delivery of therapeutic plasmid DNA to the inflammation site to transfect cells so that they can take over producing the drugs at the site.

“Oral gene delivery for efficient transfection is the holy grail with potential to treat many different diseases” said Amiji. “Our proposed method is a clinically translatable option for IBD treatment that offers a very high patient-compliant therapeutic approach and promises to eliminate frequent invasive administration of drugs with strong side effects.”

Funded by the grant, Amiji’s research will be conducted over four years. The research team also includes as co-investigator, Dr. Akio Ohta, Assistant Professor of Pharmaceutical Sciences at Northeastern’s and a member of the New England Inflammation and Tissue Protection Institute, and as consultant, Dr. Takeshi Sano, Associate Professor of Radiology and Director of the Center for Molecular Imaging, Diagnosis, and Therapy at Beth Israel Deaconess Medical Center and Harvard Medical School.

For more information, please contact Renata Nyul at 617-373-7424 or at r.nyul@neu.edu.

About Northeastern

Founded in 1898, Northeastern University is a private research university located in the heart of Boston.  Northeastern is a leader in interdisciplinary research, urban engagement, and the integration of classroom learning with real-world experience. The university’s distinctive cooperative education program, where students alternate semesters of full-time study with semesters of paid work in fields relevant to their professional interests and major, is one of the largest and most innovative in the world.  The University offers a comprehensive range of undergraduate and graduate programs leading to degrees through the doctorate in six undergraduate colleges, eight graduate schools, and two part-time divisions.  For more information, please visit www.northeastern.edu


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