In what ways might your project benefits society?

How might your solution to one problem lead to other problems (e.g. social/political/ecological)? How can you anticipate and address these issues? The way our project could help benefit society is that it offers a possible treatment option using promising genetic engineering methods to people across the world suffering with A1AT deficiency and other substitution point mutations. Other examples of deleterious substitution point mutations include sickle cell anemia and cystic fibrosis. Our project combines two new genetic engineering methods to help allow the release of anti-trypsin among people suffering A1AT deficiency, first using of CRISPR CAS9 to “cut out” the single base pair mutations. We will then, beginning from next year, focus on putting the fixed genomes in organ buds comprised of iPS stem cells. After the organ buds have multiplied and activated the fixed genomes, there will be the transplantation of the organ bud into any part of the human body that connects through the bloodstream. Thus, in the case of treating A1AT deficiency, this will allow for the release of antitrypsin so that the body will not succumb to cirrhosis and lung damage. Over time, we believe if the implantation with the substitution point mutation were to be successful, we would be able to treat any genetic disorder, if the disorders genetic abnormalities have been mapped. Our project helps society because it is a long term solution that will be able to have less often visits to the doctors/hospitals compared to other therapies, such as the replacement therapy. Other problems our solution may lead to Since research regarding iPS cells is fairly new, we may be met with challenges of not being knowledgeable enough. Moreover, there are some ethical problems revolving around the usage of iPS cells. With the wrong motive, it can be used to clone organisms.

Which communities may be most interested or most affected by your project?

Which communities may be left out or negatively impacted if your project succeeds?

The fact that our solutions target genetic mutations especially relates to the community. Many genetic mutations are passed down for generations. For example, 25% of children will inherit cystic fibrosis if they have two carrier parents. Genetic mutations also have the potential to affect ethnic communities. For example, 1 out of every 365 Black or African births have sickle cell anemia . The direct effect genetic mutations have on families and communities further strengthen the importance of focusing efforts on genetic diseases.

How might you get feedback on the viability and desirability of your approach?

How will you incorporate this feedback into your project design and execution?

Feedback has been a crucial part of our process. In fact, feedback made us completely change our whole direction from first wanting to work with using iPS stem cells to help support endangered or revive extinct animals. Through working with Dr. Kagimoto, the CEO of Healios , a company working with using stem cells regarding macular degeneration he was able to help guide us to using organ buds and working more closely related with genetic conditions. He has not only given us the resources to work with organ buds the following year, but has also given us insight on Japanese regulations and health care system.

We also worked on gathering advice from other iGEM teams using SurveyMonkey. In our survey, we asked a number of questions regarding the use of genetic engineering for medical therapy. From SurveyMonkey, we were able to obtain a wide variety of insight from other countries, including Pakistan and Mexico. Most countries had similar responses, that as long as genetic engineering was not used for aesthetics and was solely used for therapy that their culture and ethics agreed with the practice.

How might current regulations apply to your project? Are they sufficient, and if not, how might they be changed?

Current regulations may apply to our project in the context of the usage of iPS cells and embryonic cells. Our ultimate goal of this project is to be able to apply the technology in humans, so we would need to use both iPS cell and ES cell technology before being able to do so. Currently, the regulations regarding iPS cell technology in Japan and in the U.S., where we would most likely test our project, are relatively loose. IPS cell technology does not have nearly as much controversy regarding its ethics as ES cell technology, due to the fact that there is less ethical debate around the subject matter. These looser regulations would allow us to make adequate progress. We feel that the regulations are sufficient since both countries require the consent of the subject who the cells are derived from.

How might your approach compare to alternative solutions to the same or similar problems (including approaches outside of biotechnology)?

Because there are no direct treatments available that appropriately target PIZZ associated diseases, current efforts to combat A1AT Deficiency are limited to liver transplantation and supportive care. Though lung transplantation can more than double the survival rates of those carrying the ZZ genotype, the scarcity of donors and increased risk for infection and rejection by the body hold this option as unrealistic and unlikely to be considered a global method of treatment. Alternatively, other methods of treatment deal with the specific conditions commonly caused by A1AT, such as COPD (Chronic Obstructive Pulmonary Disease). A1AT augmentation therapy is another path of treatment where A1A1 infusions are conducted, increasing levels of A1AT in your body in order to slow down the progression of COPD and lung destruction. Currently, there are four commercial augmentation products that are FDA-approved. However, this treatment is solely preventive rather than curative, which means that it must be put and kept in effect immediately after the disease is detected. In addition, trials show varied results in terms of how effective augmentation therapy is to increase survival rates. The aforementioned treatment methods, though proving helpful in some aspects, are limited by the hereditary nature of the disease they are targeting.

Sources

Mutation
Alpha-1 Antitrypsin Deficiency
Nature of Mutations in Genetic Disorders
Biosynthesis, Processing, and Secretion of M and Z Variant Human al-Antitrypsin*
Treatment