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Detection, new treatment, and prevention for influenza- DNA aptamer

Inspiration

Influenza – fatal disease around the world

Influenza, so called flu, spreads around the world in a yearly outbreak, resulting in about 3~5million cases of severe illness and about 250,000~500,000 deaths.

Disadvantages of current screening

Today, we usually use antibody-type screening to diagnosis influenza. However, there are a few questions about antibody-type screening.

Firstly, the screening now has only about 60% accuracy. The high false-negative rate cause many patients leave the clinic or hospital without necessary treatment which makes the disease keep spreading.

Secondly, the cost of the antibody-type screening test paper is high. The clinics or hospitals in remote districts and developing countries may not have sufficient resource to afford the expense.

Thirdly, the production of antibody requires specialized environments, instruments, techniques and supervisions. It also takes long time to test the accuracy. When it comes to newly infectious type of influenza, it may be too slow to meet the urgency. Therefore, developing simple and accurate rapid diagnostic methods is important.

Last but not least, the added value of current rapid screening system is not enough. If all the collected data can be transmit to an integrated Cloud database, the government can utilizing the data through algorithm programing such as the AI system that is all the rage. In the view of public health, the potential for preventing the disease expansion is promising.

SELEX and aptamer - a better choice

Special characteristics of aptamer

Aptamers, which are short single strand DNA, possess high affinity to molecules with no limitation such as toxins and chemical particles. The wide-ranging affinity is due to its high variability of its two dimensional structure. The binding principle of the aptamer is the configuration With a method called SELEX (systematic evolution of ligands by exponential enrichment), we can get the aptamers which have high affinity and specificity to the target molecule from a random aptamer pool. By using this method, aptamers can act and be used as single colonial antibodies. Compared to single colonial antibodies, aptamers have higher stability toward heat and there is no need to sacrifice animals to produce aptamers. Moreover, due to their smaller size and being non-immunogenic, aptamers have the potential of becoming a therapeutic tool to treat different diseases. Additionally, it lowers the price and takes shorter time to develop and produce aptamers when comparing to single colonial antibodies, making it easy to maintain the supply and demand when the flu epidemic breaks out.

SELEX- amazing method to get aptamer

Researchers usually use a method called SELEX (systematic evolution of ligands by exponential enrichment) to select aptamers we want from a random aptamer library. By repeating amplifying the product and doing the next SELEX, we can finally get aptamers with highest affinity to our target.

CSMU_Taiwan Influsystem - a model of future screening

We use SELEX to find aptamers which can bind the influenza virus and its subtype. We also design a system to integrate the advantages of the aptamer. With this system, we can use aptamer as tools of screening, prediction, prevention and treatment.

Screening

aptamer-type test paper-
Since the time it takes to select out aptamers is much shorter than antibody, we are able to make a novel and fast screening tool when facing emerging infectious disease. Also, the price is cheaper and the test paper easier to store. Thus, the aptamer-type test paper can be transmitted to the people lived in remote districts that the hospital may not afford the high price of antibody. Mostly important, its low false-negative rate makes doctors diagnosis precisely and control the disease better.

Prediction

AI system-
By collecting the big data of virus through air purifier and the test paper, we can provides training data for the AI system to help us predict the trend of the virus spreading. It will help us to predict the outbreak of the disease. To countries which cannot offer free vaccine or is too large to take care of all the citizens, the spreading trend of disease will help the government to use the resource efficiently.

Prevention

Air purifier-
We design an air purifier which has a chip of aptamer that can sense and detect the virus in the air. When the droplets with virus are in the air, the virus will connect the aptamer on the chip, and then the connection will change the electrical characteristics. Next, the air purifier will give us the warning and we can take preventive measures immediately.
Because the air purifier can sense whether the environment is soaked in high concentration virus or not. We can take preventive measures against the virus if we receive the alert from air purifier. Furthermore, the data collected by the air purifier can be transmitted the Cloud database. With large amount of collected data, we can make a more accurate prediction through AI system.

anti-hemagglutinin drug-
We can spray the anti-virus spray containing the selected aptamer with sprayers or air coolers to the enclosed places where the concentration of virus may be high. The aptamer in the droplets will catch the virus in the air and neutralize the virus. The aptamer spray is stable in the room temperature and thus easy to store and use whenever we need it.

Treatment

Anti-virus spray-
Aptamer can act as an inhibiter to proteins, so we have the idea of anti-hemagglutinin drug.
We are trying to find aptamers which can bind to the hemagglutinin of influenza and block its ability to invade cells.
If it works in human body, it can become a new choice to treat patients infected by influenza.

References and sources

1. Li, W., Feng, X., Yan, X., Liu, K., & Deng, L. (2016). A DNA Aptamer Against Influenza A Virus: An Effective Inhibitor to the Hemagglutinin–Glycan Interactions. Nucleic acid therapeutics, 26(3), 166-172.
2. Shiping Song, Lihua Wang, Jiang Li, Chunhai Fan, Jianlong Zhao (2008). Aptamer-based biosensors. Elsevier. doi: 10.1016/j.trac.2007.12.004
3. Subash Chandra Bose Gopinath (2007). Methods developed for SELEX. Analytical and Bioanalytical Chemistry.
4. Regina Stoltenburg, Christine Reinemann, Beate Strehlitz (2007). SELEX—A (r)evolutionary method to generate high-affinity nucleic acid ligands. Elsevier. doi: 10.1016/j.bioeng.2007.06.001
5. Guo, K., Wendel, H. P., Scheideler, L., Ziemer, G., & Scheule, A. M. (2005). Aptamer‐based capture molecules as a novel coating strategy to promote cell adhesion. Journal of cellular and molecular medicine, 9(3), 731-736.
6. Xiaoge Hu, and Xiaohu Gao.” Multilayer coating of goldnanorods for combined stability and biocompatibility” Physical Chemistry Chemical Physics, issue21, 2011
7. Kratschmer C, and Levy M. “Effect of Chemical Modifications on Aptamer Stability in Serum.” Nucleic Acid Ther. 2017 Dec;27(6):335-344
8. Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017. Lancet Respir Med. 2019 Jan;7(1):69-89.