Team:ZJU-China/Description
ABSTRACT
Hepatic cancer has already been a severe public health problem to be urgently dealt with in the whole world. Traditional treatments including surgery radiotherapy and chemotherapy are not satisfying in hepatic cancer treatment due to their side effects. Therefore, we decided to develop a new type of oncolytic virus to treat hepatocellular carcinoma (HCC). We use RNAi as our weapon to kill malignant cells and eliminate possible virulence caused by oncolytic viruses with several safety designs which make virulent virus turns into a guard. Moreover, we also increase the specificity of the virus to target tumor cells and reduce the early clearance of virus by patient's immune system.
DESCRIPTION
Why we decided to create ViruGuard ?
ViruGuard is the name of our oncolytic virus, which carries our hope of swithching the virus into a brave fighter against the tumor. With the strong weapon, RNAi mechanism, the oncolytic virus gained the ability to efficiently kill cancer cells. Besides, we also noticed that the virulence of virus was a double-edged sword, so we had spent great effort to increase the safety of our product. To achieve this goal, we designed several parts to restrict how virus would militate and these methods were shown in our wiki.
However, we are not satisfied with only developing a possible theoretic treatment method for hepatic cancer. The complex environment and the interaction between the tumor and virus will add so much uncertainty into clinical application. To have a comprehensive understanding of how the virus will interact with the human body, based on the published data, we had developed a model which mimicked the oncolytic process. This model illustrated the dynamic change of the whole process and proved the efficiency of our project in a mathematical direction.
Moreover, treatment is not the only way to fight against the tumor, early diagnosis is another direction. Earlier the tumor is found, more hope is given for treatment. Our product can not be applied without a reliable diagnosis. Therefore, we had developed a bioassay chip that could detect the specific sign on hepatic cancer cells. This method is easy-to-use, requiring only a small amount of tissue or even blood. Meanwhile, it is also a low-cost method, allowing early screening.
Lastly, if the products are not able to be used in clinical practices, our goal of improving the situation of HCC patients will only be an armchair strategist. We had conducted a full evaluation of the feasibility of the project in our human practice which provided robust support for the future development of our project.
All in all, every part of our project, no matter the wet or dry lab or human practice work has an organic interaction with each other. The collaboration gives ViruGuard continuous improvement throughout the year.
Inspiration
Before confirming the topic, the students of ZJU China, by fully understanding the requirements of the iGEM competition and the original intention of ZJU_China to participate in the competition, determined that the project we were going to work on in this competition must be closely related with the problems urgently needed to be solved in our country and society, and we can provide solutions to these problems that have plagued the people around us for a long time. Therefore, we conducted a one-month brainstorming, during which the topics raised covered environmental protection, resource regeneration, daily life, diagnosis, treatment and etc.
While we were discussing the selection of projects, a famous Chinese character, Wu Mengda, who had brought happiness to generations of people, passed away because of hepatic cancer.
This news led our attention to the topic of "developing new methods to treat liver cancer". Hepatic cancer has a large population base in China, incidence rate and mortality of which is always one of the highest in the world. And it is the most common cancer type causing the most death in China in 2020.[1] Therefore, we want to use synthetic biology to establish an effective treatment method for liver cancer.
Background
There are diffrent kinds of liver cancer, so after initial investigation and research, we focused on primary liver cancer, namely hepatocellular carcinoma (HCC). It is one of the most common malignant tumors in China, which is often led by aflatoxin exposure or the evolution of viral hepatitis. The dietary characteristics of Chinese[2] and the huge population of hepatitis B patients are the reasons for the high incidence of this kind of liver cancer in China. All the information collected indicate that the hepatic cancer is a problem demanding new solutions.
Current solution
The traditional ways to treat the hepatic cancer includes surgery and radiotherapy.[3] Chemotherapy will cause great burden to the liver and other organs, and most types of hepatic cancers are not sensitive to chemotherapy, so this type of method is not an optimal way in hepatic cancer treatment. Some researches have already discovered the survival influence of radiofrequency aAblation and surgery resection on HCC patients. The result is not optimistic, with only around 20% of 5 years survival rate for RFA and 50% for resection [4]. Therefore, we had conducted further investigation, it was found that the concept of "oncolytic virus" had also been paid much attention to in the past ten years. So oncolytic virus may be another way to achieve a better long term survival rate in HCC patients.
The situation of oncolytic virus research
Quite a lot oncolytic virus researches has been done in the past 10 to 20 years, and most of them only used a single mechanism for treatment or were only concerned about one aspects of the tumor treatment. Besides, most of the oncolytic virus remained in the pre-clinical stage and there were only several products were approved. In the pre-clinical studies, we found that a lot of them focused on the treatment of HCC while in clinical stage studies we could hardly find any oncolytic studies being carried on. [5].
Therefore, we concluded that HCC oncolytic virus is a problem demanding prompt solution. Moreover, all the clinical-stage oncolytic virus had shown side effects and some may cause great damage to the patients. These surveys showed that our idea of designing a HCC oncolytic virus was significative and the aim of increasing the safety of the product was meaningful.
Our solution
We decide to increase the safety of the oncolytic virus and improve its efficiency by combining several mechanism together to realize the treatment purpose. We name our product 'The ViruGuard', hoping the virus can become a guardian to fight against the tumor.
References
[1]Sung Hyuna,Ferlay Jacques,Siegel Rebecca L,Laversanne Mathieu,Soerjomataram Isabelle,Jemal Ahmedin,Bray Freddie. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.[J]. CA: a cancer journal for clinicians,2021,71(3):
[2] Jian Yaowen, Xiong Wenjing, Liu Ye, Liu Yang, Yang Huixian, Rang Weijing.A meta analysis on relationship of dietary factors with liver cancer in chines population[J].Cancer research on prevention and treatment,2017,44(07):493-500.
[3]]Rahul Rajeev,T. Clark Gamblin,Kiran K. Turaga. Hepatic Perfusion Therapy[J]. Surgical Clinics of North America,2016,96(2):
[4] Alfredo Guglielmi,Andrea Ruzzenente,Alessandro Valdegamberi,Silvia Pachera,Tommaso Campagnaro,Mirko D’Onofrio,Enrico Martone,Paola Nicoli,Calogero Iacono. Radiofrequency Ablation Versus Surgical Resection for the Treatment of Hepatocellular Carcinoma in Cirrhosis[J]. Journal of Gastrointestinal Surgery,2008,12(1):
[5] Tenneti Pavan,Borad Mitesh J,Babiker Hani M. Exploring the role of oncolytic viruses in hepatobiliary cancers.[J]. Immunotherapy,2018,10(11):
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