Team:SJTU-BioX-Shanghai/other

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• Safety Issues
• Collaboration
• Human Practice

Safety Issues

• Please visit our safety page for details.

Collaboration

• Summer event:
  • As the host, we sucessfully held the iGEM 2010 China Meetup. Please refer to that page for details.
• Collaboration with team ECUST-Shanghai:
  • On May 19, four of our team members set out to have a collaboration event with the freshman team ECUST-Shanghai. We exchanged ideas and plans, and had a good time making friends with each other.
  • In July, ECUST team have met problems with their experiments. We helped them debugging their design, and eventually found the problem lying in the quorum sensing system. The QS signal sending and receiving parts they used were of poor quality, including LuxR, LuxI, CinR, CinI, rhlI, rhlR, and several reporters. We again helped them by offering them our own LuxR and LuxI parts. This solved a big problem for ECUST-Shanghai, although they may probably not come to the Jamboree. (what a pity!)
  • Photos taken during our collaboration:

Human Practice

Introduction

As our project this year aims to develop a new therapy, we think public recognition and acceptance is an important part. So we designed a questionnaire and conducted a survey to get an overview of opinions on our new OA therapy. Here are some photos we took during one session of our whole survey.

Note:

• The survey was carried out in undergraduate students in biology-related majors, as we thought understanding the whole project may require some background knowledge. We could have conducted similar surveys among common people (regardless of age, education, profession, etc.) if only we had more time.

• The original survey was conducted in Chinese for participants’ convenience and accuracy of results. The questionnaire is translated into English and you can download it here.

Data and analysis

We received 97 valid answers, and the statistic result can tell us something about people’s opinions.

In the general background part, all of our participants have heard of gene therapy before and believe it’s possible to cure OA through gene therapy. This result shows that the recognition of gene therapy in this group is relatively high.

When comparing gene therapy and traditional therapy, most students think treatment efficacy (87.6%) is the biggest advantage, and safety (97.9%), as we expected, is their biggest concern. Though all the students thought curing OA is possible, 35.1% of them agreed that the side-effects brought by gene therapy will be a more serious problem. When asked whether they will choose gene therapy if its cure rate is 2-3 times higher than traditional therapy with all other condition equaled, the answer is about 50%-50%. Because gene therapy is not mature now, they worry about potential safety risks.

As to opinion on safety issues, interruption of patient’s genome, risk of insertional mutagenesis or even carcinogenesis concerns the participants most(47.4%), followed by doubt on effects and control of the gene circuit(25.8%). To our surprise, the answer doesn’t show preference on E.coli or virus vectors(35.1% for E.coli and 34.0% for virus), and 30.9% of them think neither of vectors is safe in treating OA. We proposed several solutions to improve safety, 51.5% of them think replacing the virus vector or use non-integrated virus vector should be the first step. The other half agree on the importance of other factors such as quantity control and antigen removal, which we’re working on.

Conclusion

Nowadays the concept of gene therapy is promoted in public, though it’s still theoretically possible with a few successful cases. Safety risk is still the biggest problem, and people know that. In the strict sense, our project is not the typical gene therapy that corrects the abnormal gene; we combine synthetic biology with gene delivery and expression to generate curing effect—it’s more accurate to call it “therapy using genes”. However, we may face some same problems in authentic gene therapy, such as viral vector problem, tumorgenesis, and multigene disorders (specificity problem). Also, the regular problems of synthetic biology application may exist such as immune response and how to control the circuit. We come up with corresponding solutions to minimize safety risks and hope further advancement in this field could better our job.

1. Specificity issue: In eukaryotic part, we use tissue-specific promoter GDF-5 and light-controlled switch ChR2 to ensure the curing gene only be expressed in chondrocytes with specific light exposure. In prokaryotic part, the “detector” employs inflammation factor like NO and hypoxia signal to detect the location and activate the downstream gene expression.
2. Immune issue: As long as a foreign object is introduced into human tissues, the immune system will attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a possibility. To reduce immune response, we plan to remove the antigens on bacteria/virus. Details regarding E.coli antigen removal could be found in *** team’s project in 200* iGEM.
3. Control issue: We expect the circuit to stop functioning or commit suicide once it has accomplished its curing mission. Our OA-curing E.coli has the “supervisor” part, which employs the quorum sensing system to control bacteria density—both over-population and injection of inducer will lead to suicide and removal of bacteria. In eukaryotic part, light exposure is a must for the activation of whole system, while tissue-specific promoter GDF-5 controls the switch of downstream circuit as the second guard. Once the treatment is over, the process can be easily switched off by removing the light exposure. And we have conceived a feedback inhibition by adding Cabin1 at the end of the circuit, which will act upon MEF2 once expressed under certain condition. We have confidence controlling the therapy won’t be a problem.
4. Vector issue: E.coli, the most widely used prokaryotic engineered bacteria, still have safety and other issues. Apart from antigen removal and other efforts to minimize its risk, replacing it with a more human-friendly kind of bacteria (such as bifidobacteria, advised by a professor from medicine school) may also be a choice. In eukaryotic parts, viral vector is the biggest problem and most difficult to answer. Up to now, there isn’t good solution—though many vectors available such as retrovirus, adenovirus, and non-viral methods, they all have their own drawbacks that prevent further clinical trial. So there is still a long way to go until our therapy can make real difference on human body. As our project only involves the circuit construction and function test in this stage, vector issue won’t be a big problem now. We believe this problem will be solved with further advancements in gene therapy.
5. Others...: It requires great time and efforts to accomplish these improvements, and progress in science and medicine will give rise to better solutions. So the realization of our project might not be just a dream in the near future.