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 was 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 outside voices when doing researches. For just standing on others’ shoulders will lifted a project a lot. This part contains:

Consultation with expert

Staying in the lab won't let us know what technical issues of production and circulation should be considered, 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, and we interviewed on it. Click here to see more information of the interviews.

Cooperation among groups:

In the end of August, we attended Conference of China iGEAMer Community, idea exchange meetup for China region.click here to see what we have done!

Part two: Bear social responsibility

This year our project is to develop a novel approach for miRNA inhibiting, but that is not all. As an integrated project, in addition to pure research, it has several tasks needed to be done in practice:

Open that black box

Scientific research has never belonged to only a few people; we are responsible for science popularization of our product and its related contents. This year we did something different! 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 mentioned how to standardize the microRNA antagonist therapy has been made, so we will have to wait for it, however, we consulted professors and had a general idea of policy. 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. Song Zhuo. As the CTO, he really considered more than we students, which inspired us a lot.

The most important point we realized lies on safety. If a product or a technology is put into use, the very first thing is to ensure its safety. Thus, he 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; 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, 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 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, we managed to contact with 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 different medical universities.

Li Ling is a Professor and master’s supervisor of biochemistry and molecular biology department, school of Basic Medical Sciences, Southern Medical University, his main research direction 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 phase three clinical trials. MicroRNA and its antagonist therapy is a promising new technique for treating diseases at gene level. With the wide application of this technology in clinic, many clinical drugs and therapies harmful to human body will disappear. However, new therapies will have their own advantages and shortcomings, and old things cannot fade away immediately, new things will also face many challenges to retain. 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 serve the 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 not mature? How about the acceptance of these risks?

A:Obviously, microRNA antagonists can treat diseases from the source 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 described, some of the side effects associated with new therapies also exist. There may be individual differences, and there may be some deficiencies need to be improved. 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.

Tu Shuo 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: MicroRNAs are more used in early cancer detection at present, 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 patient's genetic sequence. Gene therapy is nothing more than 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 not mature? How about the acceptance of these risks?

A: Liver toxicity depends on whether the drug itself is toxic or only after metabolized in vivo, or it is only toxic 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.so once something unexpected happens, we can stop using the drug or replace therapeutic plan. There are many drugs have liver toxicity, so the drug can still be used in clinic even it has liver toxicity.

Cooperation among groups

In 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 a year before, then we decided to offer 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 has some relevance to our project; 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. Thanks to CCIC, it 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 teams’ project mechanism, new situations encountered in experiments and progress of modeling and human practice.

Open that black box

Publizing with new media

This year our track is foundational advance，and the product---miRNA inhibitors is not familiar to the public. Therefore, if we want to have the public engaged in our work, the very first thing 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 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 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 acquire the effectiveness of the publizing conveniently 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, like me, will probably feel bored to read something contain nothing but words, especially when the words is about learning. I realized it after I entered college to find there are too few illustrations in textbooks. 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.

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Lecture in high school

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

Last year, our team had Lab open day for some high school students. One named Zhang Herui, showed great interest in iGEM competition and synthetic biology and was recruited into our team. This year, 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. Also the popularization of synthetic biology is achieved.

Attentions on policy-making

MiRNA antagonist therapy is a brand new area that there is no policy to regulate it; 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 Li Ling and teaching assistant Tu Shuo on wht should be paid attention to 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

Team:NUDT CHINA/HP/Silver

Silver

Part one: Absorb nutrients from the outside world