$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​.north​eastern​.edu.