Team:NUDT CHINA/HP/Silver

Silver

Scientific researches and the public should not be separated; in fact, there are close interactions between them. It is hard for a product to serve human well if it is made in a closed door.

Part one: Absorb nutrients from the outside world

Many Chinese students are taught to study alone in order to avoid external disturbances, but it is better to listen to different voices when doing researches. As the proverb goes, "If I have seen further, it is by standing on the shoulders of giants." The same is true for a bio-synthetic project. This part contains:

Consulting an expert

While staying in the lab won't let us know what technical issues are of consideration by production and circulation, an experienced CTO of a biology company can offer really useful advice. Click here for more details!

Product evaluation

We investigated similar products available on the market, and evaluated our product. Click here to see what makes our product stand out in the market.

Interviews concerned on important application fields

Our project is mainly for academic uses. However, miRNA inhibitors’ role on medical treatment cannot be ignored. Therefore, we conducted interviews about it. Click here to see more information of the interviews.

Cooperation among groups:

At the end of August, we attended Conference of China iGEAMer Community, an idea exchange meet-up for China region.click here to see what we have done!

Part two: Bear social responsibility

Our project this year is to establish a novel approach for miRNA inhibiting, but that is not the whole picture. As an integrated project, our work has far more practical tasks and aims than just pure research:

Open that black box

Scientific research has never belonged to only a few people; it is our responsibility to popularize scientific knowledge and information related to our project. This year we did something interesting and unique! Click here to check them out.

Moving our glow sticks for synthetic biology

Participating in a synthetic biology competition, we wanted to exchange our ideas on synthetic biology with other interested schoolmates, thus we gave a presentation carefully prepared to them. Click here for detail.

Attentions on policy-making

So far, no policy has been established on how to standardize the microRNA antagonist therapy, Instead of simply waiting for the new policy, we actively consulted professors and obtained a general idea of it. Want to see? Click here.

Consultation with expert

We went to GenetalksGenetalks is founded in Santiago by a team of young scientists in North America. Since 2009, the clinical transformation of gene testing has been carried out, and it was formally established in Beijing in 2014. With the core of gene technology and other advanced technologies such as information technology and machine learning, the company is committed to technological innovation, application development and services in the field of medicine and health. hoping to receive some professional, market-based suggestions from technicians there, and we were lucky enough to interview Dr. Zhuo Song. As the CTO, he really formed a deeper idea than we students, which inspired us a lot.

The most important point we've discussed was about safety issues. If a product or a technology is put into use, the very first thing is to ensure its safety. On this thing, Zhuo put forward two questions:

  • Will the sponge affect the normal function of cells?
  • Will MicroRNA inhibitor work in positive correlation with level gradient?
  • These provided us new ideas of safety inspection of product beyond the mainline; in order to fully solve these questions, we added cytotoxicity test and concentration gradient experiment to our future work.

    As for application, he mentioned the market of MicroRNA inhibitor is not limited to research or the treatment of human diseases. Actually, agriculture and animal husbandry are also potential and untapped areas for MicroRNA inhibitor. Moreover, market sense is also important for a project; a streamlined and efficient experimental method, along with a lower cost, will make our project more popular.

    Product evaluation

    We evaluated the cost of our product. It contains mainly three steps:

    1. Major Instruments and Reagent

    (1)Reagents

    Oligo, EcoR I, Spe I, T4 Polynucleotide Kinase, T4 DNA ligase, DH5α, 2×Tap Master Mix, Tiangen Plasmid Microkit Kit.

    (2)Instrument

    Since the instruments needed for synthetic locker are the most common in the lab, they are not included in the evaluation.

    2. Experimental Procedure

    Click here to see the protocol

    3.Cost Evaluation

    Name of reagents

    Unit price

    Use level

    Equivalent

    Price for per-million cells

    Oligo

    $0.12 / base

    0.00254 bases

    $0.000302

    $0.00114156

    EcoR I

    $19.55/4000U(15U/µL)

    0.1µL

    $0.0073

    $0.027594

    Spe I

    $19.55/150U(10U/µL)

    0.1µL

    $0.13

    $0.4914

    T4 Polynucleotide Kinase

    $25.87/200U(10U/µL)

    0.2µL

    $0.26

    $0.9828

    T4 DNA ligase

    $25.87/28000U(350U/µL)

    1µL

    $0.32

    $1.2096

    2×Tap Master Mix

    $102.27 / 5mL(3 pieces/mL)

    10µL

    $0.05

    $0.189

    Tiangen Plasmid Microkit Kit

    $102.27 / 200 times

    One time

    $0.51

    $1.9278

    The cost of our product per-million cells

    $4.83

    As a comparison to our product, we investigated similar products available on the market, contacting some companies to inquire price of their miRNA inhibitors. According to the instruction given by those companies, we calculated the cost of each products.

    Company

    Product

    Product's name

    Price

    Price for per-million cells

    Sigma Aldrich

    TuD RNA

    mission Lenti microRNA inhibitor

    $1053.27/

    $52.68

    Guangzhou RiboBio Co.

    micrOFF™ miRNA Inhibitors are synthetic antisense oligonucleotides, which is complement to mature miRNAs sequence , for loss-of-function studies of miRNAs.

    micrOFF miRNA inhibitor

    $75.65/nmol

    $37.83

    Shanghai Integrated Biotech Solutions Co.,Ltd.

    A special designed RNA molecule can bind with specific miRNA.

    miRNA inhibitors

    $76.65/nmol

    $38.33

     GenePharma Co.

    An 21-23nt RNA molecule, and was  2'-O-Methoxyethyl-Modified ,can serves as an efficiently microRNA inhibitor

    GMR-miRTM microRNA inhibitors

    $105.91/nmol

    $52.96

    Biomics Biotechnologies.

    This is a miRNA inhibitor, which is especially chemical modified, so that it can serves as an efficiently and specifically inhibitor.

    miRNA inhibitor

    $98.35/10nmol

    $ 1.02

    BIONEER Trade(Shanghai) Co.,Ltd.

    This specially designed RNA molecule, which has been specially modified, can bind with specific miRNA.

    AccuTarget™ miRNA Inhibitor

    5 n mole

    $55.68

    $1.16

    10 n mole

    $84.31

    $0.88

    20 n mole

    $108.40

    $0.57

    Interviews concerned on important application fields

    Nowadays, miRNA inhibitors play an important role in medical treatment. To know more information of miRNA antagonist therapy, we interviewed a professor and a teaching assistant from two different medical universities.

    Ling Li is a Professor and master’s supervisor of biochemistry and molecular biology department in school of Basic Medical Sciences, Southern Medical University. His main research focus is molecular mechanism of bone metastasis in tumor.

    Q: A major application direction of our project is microRNA antagonist therapy. What impact do you think it will bring to the basic treatment? And what new challenges will it pose to hospitals and doctors?

    A: News showed that the FDA program approved gene therapy technology and the first gene therapy was expected to be approved in January 2018. In addition, an RNAi (RNA interference) drug has entered the main clinical endpoint of third phase clinical trials. MicroRNA and its antagonist therapy are promising new techniques for treating diseases at genetic level. With the wide application of this technology in clinic, many harmful clinical drugs and therapies will be eliminated and replaced. However, new therapies will have their own advantages and shortcomings. While old things cannot fade away immediately, new findings will also face many challenges to retain their own status. Hospitals and clinicians should keep up with the breakthrough of medical technology, enrich the knowledge reserve of gene therapy technology and its treatment, and meet the new challenges at any time to promote human health.

    Q: Systematic drug-given method of the current microRNA antagonist therapy may induce adverse consequences, such as complement activation, hepatotoxicity, and so on. Do you think that means that this therapy is still immature? How about the acceptance of these risks?

    A:Obviously, microRNA antagonists can treat diseases from the very beginning by inhibiting the expression of target genes at the gene level, and have shown good efficacy in a large number of clinical studies and clinical trials. As you have described, some of the side effects associated with new therapies also exist. There may be individual differences, and there may be some deficiencies that require further improvements. When the microRNA antagonist therapy enters clinical trials and FDA (sFDA) approval process, the treatment effect and its risk will be evaluated, and then mature therapy will be approved. For the new treatment, the patient's acceptance may be different, most of them need to be informed before the medication, and it is necessary to sign the informed consent.

    Shuo Tu is a Teaching assistant of biochemistry and molecular biology department of Nanchang University, and her main research direction is tumor cell apoptosis.

    Q: what role do microRNAs play in medical treatment nowadays?

    A: Although microRNAs are currently used in early cancer detection in most cases, they may appear as adjuvant treatment in the future.

    Q: What new challenges do you think microRNAs antagonist might pose to future medical scheme design?

    A: The most important challenge is personalized care. It would be ideal to design treatments based on the patients' genetic sequences. Gene therapy is nothing more than just specificity, so the key is to find the most specific impact factors or biomarkers of disease, and change it to reach the therapeutic effect of disease. Therefore, the effect of antagonist treatment is determined by whether the first stage can find the key target.

    Q: Systematic drug-given method of the current microRNA antagonist therapy may induce adverse consequences, such as complement activation, hepatotoxicity, and so on. Do you think that means that this therapy is still immature? How about the acceptance of these risks?

    A: Liver toxicity depends on whether the drug is toxic itself, before or after metabolization, or it is toxic only to the individual populations. If the drug itself is toxic or metabolized to produce toxicity, then it is necessary to control the dosage strictly and conduct periodic blood biochemical examination during the drug use. As for complement activation, make clear whether it is due to individual specificity or universal situation. It can be taken simultaneously with drugs that inhibit complement activation or optimize its structure. In this way, once something unexpected happens, we can stop using the drug or replace therapeutic plan. It is common for currently used drugs to have liver toxicity, so the drug can still be used in clinic regardless of its liver toxicity.

    Cooperation among groups

    At the end of August, we attended FAFU_CCICFujian Agricultural and Forestry University Conference of China iGEAMer Community, and spent three days there.

    The meetup is held for teams to share ideas and help each other. When communicating with other teams, we heard team BGIC-Union need plasmids which we designed last year. Upon this realization, we decided to offer them the plasmids, click here for details in collaboration page. In a few words, we had a fulfilling time in CCIC!

    Exactly at this meeting, we found the project of team Lanzhou is relevant to our project in some extent; their project is A novel method in controlling weeds and pests by tandem RNA Interference. Then we made communication in specific experiments at the venue. We want to express our greatest thanks to CCIC, which provided a nice platform for teams to get together, know each other and discuss the possibilities of cooperation.

    After CCIC, we made deeper online interaction with team Lanzhou with more team member participated.

    In this online interaction, we talked about each team's project mechanism, newly encountered situations in experiments and progress of modeling and human practice.

    Open that black box

    Publizing with new media

    This year our track is fundamentally advanced. Because our product--miRNA inhibitors--is not familiar to the general public, our necessary first step to get public engagement is to let them make friends with miRNA and our project!

    In order to achieve a greater influence and outreach, we decided to have our popular science article pushed forward by WeChat subscription (The WeChat ID of the subscription account is zaxue8. It aims to spread knowledge to the masses). In addition, we used many internet memes in this article for a more vivid expression, and it worked just as we had expected!

    By now, 2666 people have read this article, and the number is still increasing. Since it is on the internet, people can open it without limitation of time and space. And we can easily acquire the effectiveness of publication by reading rate and top comments.

    You can read the article below as well as scaning the QR code by WeChat to read our articles on your phone:

    Since we estimate miRNA is not popular among masses, we attached a small survey at the end of the article, and the result is:

    This chart shows that the miRNA popularization still has a long way to go, and it might take a long time before taking the second step.

    Do you want a picture book?

    Many people feel bored to read something contain nothing but words, especially when the words is about academics. After entering college, I realized that the illustration is textbooks are too limited. We do not want others to feel the same when they try to read our pamphlets, so we made it a beautiful picture book, printed and separated.

    Lecture in high school

    High school students are young, vibrant, and always open to new things.

    Last year, our team had a Lab Open Day for some high school students. One student named Zhang Herui showed great interest in iGEM competition and synthetic biology and is recruited into our team this year. For this year's project, considering there are few references of miRNA mentioned in textbooks, we walked into her school to fill the blanks and introduce our project.

    Moving our glow sticks for synthetic biology

    In June, our team was invited to give a lecture on iTED Sharing held by the Squirrel Club of NUDT. The theme of the lecture is biotech 2.0-the synthetic biology and iGEM in my eyes. Through this lecture, we gave the present students an introduction of our research field. We aimed to share our ideas with undergraduates and get feedbacks form the interactive section. Additionally, the popularization of synthetic biology is achieved.

    Attentions on policy-making

    MiRNA antagonist therapy is a brand new area that is in the lack of regulation policy; however, we decided to grasp the trend of policy. As the product developer, we also shoulder the responsibility of advising the government when needed. Thus, we consulted Professor Ling Li and teaching assistant Shuo Tu on things that need attention when making a policy for miRNA antagonist therapy.

    For new therapies and new technology, effectiveness and safety are two important indexes. In clinical application, there must be a strict regulation, including the indications and contraindications, and the patient's right to know. Hospital has the obligation to let patients fully understand the basic principle of anti microRNA therapy and the curative effect (cure rate) of new treatments’ individual differences, not every patient with antagonist treatment has good curative effect. The price should be transparent .

    In the design of microRNA antagonist therapy, the hospital may need to carry out specifi gene sequence measurement for patients, and the relevant confidentiality rules should be signed in advance

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