Benefitting Generations

Daniel Anderson
agrees his research may sound like science fiction: smart biomaterials, cellular-level drug delivery, genome editing, cell transplantation, and RNA interference. In fact, this work could help counter serious illnesses from genetic cancers to type-1 diabetes, both for patients and their future family trees.

Take, for example, genome editing, which provides tremendous insight under the microscope and impressive potential as a therapeutic.

“Genome-editing tools are useful for all kinds of things. In the context of what I do, they’re very useful for modeling disease, because in a lab setting you can specifically turn genes on and off and study how that effects the biology of a system,” says Anderson, the Associate Professor in Chemical Engineering and the Institute for Medical Engineering and Science.

“There’s already a phase two clinical trial at Sangamo BioSciences using (one type of genome editing called) ‘Zinc Fingers,’ where you take someone’s bone marrow out, process it, and put it back in. This is an exciting start, but I think we will reach the point where we can make therapeutic gene-editing drugs. Simply put, I expect we may be able to give someone a shot that could specifically repair a disease gene. That’s very exciting.”

Anderson’s lab at the Koch Institute for Integrative Cancer Research at MIT utilizes the latest RNA-guided CRISPR-Cas9 method of genome editing, which offers a revolutionary approach to silencing deleterious genes, such as those causing ovarian cancer or cystic fibrosis. The naturally occurring Cas9 protein is employed to precisely cut into DNA, enabling removal and replacement of a mutant gene. Anderson himself is a cofounder of CRISPR Therapeutics, a Cambridge-based company working to develop gene-based medicines.

“At MIT, we first work on the basics of certain scientific challenges, but when technology advances to the point where it can have a broader impact, commercial entities get involved. The commercial translation of technology from MIT has had a huge impact on the world” says Anderson.

In another area of research, Anderson hopes to help diabetics who experience progressive beta cell failure and destruction of their pancreases through autoimmunity.

“If you provide an exogenous source of islet cells to control blood sugar, it could be curative,” says Anderson. “Yet the immune system of type 1 diabetics kills the pancreas and would kill transplanted cells unless they are protected. Today patients receiving these transplants have to be immunosuppressed for the rest of their lives. This can lead to horrible side effects, especially for kids. Another challenge is that there just aren’t enough cells or tissues from human donors. Only a couple hundred patients get islet transplants every year out of the millions of diabetics out there.”

Anderson’s collaborator, Doug Melton, co-scientific director of the Harvard Stem Cell Institute at Harvard, has done pioneering work in growing islets from human stem cells to mass-produce an essentially unlimited therapeutic supply. Using these islets, Anderson’s group has developed a housing device with long-term biocompatibility and effective cures in diabetic rodents. (See papers in Nature Medicine and Nature Biotechnology.)

“We want the cells to function protected from the immune system, so you don’t get rejection or need to take immunosuppression,” says Anderson. “You can envision a device like a tea bag with the cells on the inside, that allows insulin and nutrients to go in and out, and blocks immune cells from killing the transplanted cells. In a way, it’s simply another medical device, but it doesn’t run on electricity and you don’t put drugs into it: it runs off of the nutrients and oxygen and makes the drugs you need on demand.”

Disrupting the molecular basis of disease is a career-long goal for Anderson, who received his PhD in genetics from UC Davis in 1997.

“I wanted to have near-term impact on medicine, so I came to Bob Langer’s* lab for my post-doc with an eye to do DNA repair therapeutically. This lead me to a broader interest in finding ways to deliver DNA and other drugs using nanoparticles, and more broadly into nanomedicine and new materials for medicine.”

Anderson says being at IMES and with the Koch Institute makes all this work possible.

“I don’t think there’s another university or company where I’d have all the tools, collaborators, and resources I need to do research on medicine in the way I’m interested. This is the best place, not only to do this sort of multidisciplinary, cutting edge research, but to think about how to translate that into the real world.”

*Robert Langer is the David H. Koch Institute Professor at MIT.