CRISPR to Make Pig-Avatars for Sick Kids

For May 2, 2018

Hi WN@TL Fans,

My quick-fire list of model organisms would include E. coli, brewer’s yeast, C. elegans, the fruit fly, the zebrafish, the rat, the mouse, and the monkey. Given more time, I’d add lambda phage, Paramecium, tobacco, corn, Arabidopsis, Xenopus, and of course the guinea pig.

But the pig itself, sui generis, probably wouldn’t make my list.  While pigs and Piglets from the pens of EB White and AA Milne are noble literary characters, a good biological model is usually small, fast, simple and cheap.  Alas, swine are about the size and weight of a human, they require some 300 days to complete a life cycle, and they take a lot of room and feed to grow.

That part about being roughly the same size as humans?  That’s where things can get interesting, because pigs could be a source of organs for transplanting to humans, if issues such as retroviruses and immuno-rejection could be managed.  Happily, the concern over retroviruses from pigs was diminished last year when researchers used CRISPR to edit out such viruses.

With CRISPR editing of DNA, there’s another possible twist:  sure, pigs might become donors, but they might also become avatars. The difference is that the avatar, being genetically edited to match critical genes in a sick child, could give us insights rather than organs—insights into how a child might respond to a medicine.

With gene editing, each individual child could have a pig tailored to be indistinguishable in certain genetic traits to those of that child, enabling the pig to be a proxy for the child in testing treatments for highly-variable diseases such as neurofibromatosis type 1. Even Fern Arable might find this another mirabile.

This week (May 2) Charles Konsitzke of the Biotech Center, and Dhanu Shanmuganayagam of Animal Science, will speak on “Pig Avatars — Patient-Specific Translational Models for Precision Medicine.”  Here’s how they describe their talk:

We will address the genetic proximity of swine to human — the overwhelming anatomical, physiological, and pathophysiological similarities — that makes swine the ideal preclinical model for studying human diseases and for developing safe and effective diagnostic and therapeutic technologies. Unlike most academic institutions where swine research is challenging, the availability of advanced swine facilities, resources, and expertise at UW–Madison — complemented by thriving biomedical and biotechnology research — has provided a clear direction for advancing a swine-centric translational research program. The recent successes in and notable efficiency of genetic engineering of swine at the UW has further refined this direction: patient-specific swine modeling (“precision research”) in the coming era of precision medicine.

About the Speakers

Dhanansayan Shanmuganayagam ’97, PhD’06 is an assistant professor and the director of the Biomedical & Genomic Research Group, which has the overarching mission of taking scientific discoveries and technologies developed by the group or its collaborators through preclinical development to clinical applications. His expertise and experience in developing and utilizing animal models in preclinical research span more than 20 years and have given him the appreciation for the translational nature of swine models. He currently leads the genetic engineering of swine at UW–Madison and utilizes the CRISPR-Cas9 platform to develop novel swine models for cancer, cardiovascular disease, xenotransplantation, and other areas of research.

Charles Konsitzke is the associate director of the UW Biotechnology Center, which focuses on campus by providing research services to hundreds of faculty members. Konsitzke has been administering and facilitating research on campus for 17 years. He has a passion for assisting the development of large-scale projects and advancing research.

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As I mentioned last week, this is the kind of work that’s hard to imagine happening at a university that doesn’t have a College of Agriculture cheek-by-jowl with a School of Medicine. Sometimes, the collaborations are even closer than cheek to cheek. For example, I didn’t realize it until Paul DeLuca gave his talk to WN@TL in 2008, but the Genetics Biotech Center building, where WN@TL is held and where I’ve worked since the building opened in 1995, is a facility of both CALS and the School of Medicine and Public Health.  The synergies are extraordinary.

Next week, May 9, the synergies are in synthetic biology as Vatsan Raman of Biochemistry shares how his research bears on biomanufacturing, the environment and human health.