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제목 [한양대신문]A Virus with Nanomaterial - The Key to Cure Cancer
조회수 4940 등록일시 2014-08-11 18:01

Yun Chae-Ok of the Department of Bioengineering is the director of the Hanyang University Gene Therapy Laboratory. She is also a well-known professor whose interests are mainly in developing gene therapy technology for the treatment of cancer. Yun studies virus modification by developing adenoviruses, and combining them with nano-biomaterials. In her paper, Enhanced therapeutic ef?cacy of an adenovirus-PEI-bile-acid complex in tumors with low coxsackie and adenovirus receptor expression, Yun discovered the DA3-coated Adenovirus which she employed to address the limitations of the existing adenovirus therapy and increase its’ efficiency to successfully treat cancer.

Yun runs an laboratory that studies gene therapy technologies such as virus modification, immunology, and nano-biomaterials in order to treat cancer.

Cancer is the leading cause of death worldwide. As a malignant tumor, cancer involves abnormal cell growth with the potential to invade or spread to other parts of the body. Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumors. They can grow and interfere with the digestive, nervous, and circulatory systems. These tumors destroy other healthy tissue and the result can be a serious condition that is difficult to treat. There are over 100 different types of cancers that affect humans. Therefore, numerous approaches, including surgery, chemotherapy, hormonal therapy, immunotherapy, gene therapy, and radiation therapy have been developed to treat it. Still, the currently available treatments do not effectively eliminate tumors. Therefore, novel therapeutic approaches are desperately needed.

Yun and her research team has developed an acid conjugated poly (ethyleneimine) (DA3)-coated Ad complex (Ad/DA3 complex). This innovative Ad nano-complex supplements the drawbacks of nano-biomaterial and adenovirus and finally creates a synergetic effect to cure metastatic cancer problems effectively.

One gene therapy approach that Yun and her research team have been extensively investigated is called oncolytic adenovirus (Ad) therapy. Oncolytic is a virus that can react to and kill cancer cells selectively. It has many advantages as a cure including the ability to self-propagate, attack infected cancer cells, and cause secondary attacks to adjacent cells within a tumor as a ‘domino effect.’ In addition, several studies have demonstrated that oncolytic Ad has engages in potent transformation and has high antitumor efficacy. Although it has various advantages as a treatment for cancer, oncolytic Ad has some disadvantages as well. First, the human body is resistant to unknown substances. So for example, when an unknown substance such as a virus enters the body, the body’s immune system reacts to the foreign invader by attempting to destroy it. Therefore, when oncolytic Ad enters body, it is interpreted as a virus intruder and the body reacts to it before it has a chance to eliminate the cancer. Second, the clinical efficacy of AD-mediated cancer gene therapy is limited due to its low level of transportation efficiency all over the human body. To cure cancer, oncolytic Ad hould spread all over the body through blood circulation and attack even unaffected areas that have the potential to be cancerous. However, the surface of Ad consists of protein, which is quite hard to circulate through the blood.

Yun has been continuing this research for years and finally figured out a strategy to overcome the above mentioned limitation. The solution is to modify the surface of Ad with a polymer. Specifically, Yun figured out a promising strategy involving the use of a chemical or physical modification of the Ad surface with polymers in non-viral systems. It may be an acid-conjugated poly (ethyleneimine) (DA3)-coated Ad complex (Ad/DA3 complex). This is an Ad nanocomplex in which the negatively charged Ad surface is physically coated with the catonic DA3 polymer via electrostatic interaction. The DA3 polymer-coated Ad complex shows increased transduction efficiency in both CAR high and CAR-negative cancer cells. The cellular internalization mechanism of the Ad/DA3 complex is different from that of naked Ad and causes an increase in the size distribution and zeta potential. The transduction efficiency of Ad/DA3 increases in a DA3 polymer concentration-dependent manner. In summary, these results prove the feasibility and potential of DA3-coated oncolytic Ad for cancer gene therapy against CAR-deficient cancer.

Yun and her team are quite hopeful of the efficacy of combined oncolytic adenovirus and nano substances. The most horrifying factor of cancer is its metastatic characteristic. For example, the cancer that settles in human organs not only infects and damages that organ but also spreads all over the body and brings serious damage to adjoining parts. The only effective cure in existence these days is chemotherapy. It is a category of cancer treatment that uses toxic chemical substances, usually involving one or more anti-cancer drugs at a time. Thus, in order to rid the body of the cancer, the toxic chemical substances should be injected in increasing amounts which ironically can cause deteriorating health. To deal with these side effects and resolve the metastatic problem, research is being conducted all over the world and experts such as Yun are paying close attention to gene therapy such as adenovirus treatment. By selectively attacking cancers, less toxic and harm to the whole body can be lessened during treatment. Moreover, when combined with chemotherapy, oncolytic Ad can bring out synergy. This combination therapy can increase the efficacy of fighting cancer cells and lessen the damanging effects of traditional cancer treatment.

 By mentioning the concept of ‘multi-displaying research,’ Yun urged her students and even pre-researchers to be open-minded as to get involved in new fields of study under the strong base of their major. She emphasized that the productive outcome of her research had been the result of her passion to learn from two different academic fields such as virus and nano-materials.

Yun runs a prestigious laboratory that focuses on the molecular biology of oncolytic Ad in order to exploit the unique features of this virus to develop an efficient viral vector and gene therapy system for use in human cancer gene therapy. Yun is famous for her research of combining viruses and nano biomaterials, which is a very different area of study and also a unparalleled research in the history of bioengineering. The success and fame of her research is a natural result considering the passion and efforts that she has been investing for over a decade. When she first started her research, others were quite skeptical because nothing similar had been done before regarding the combining of both areas. Yun started this endeavor alone in a new academic area. Following her success, the advice she would like to give HYU students who are dreaming to be successful researchers, is to be a ‘multi-displaying researcher.’ Reflect upon research trends of today which increasingly focuses on the combination and exchanges among different academic fields, she says, as she believes it is difficult to survive by insisting on one’s specific viewpoint which may actually lead to isolatation. Instead, Yun believes researchers should have an open mind toward learning and accepting different types of academic knowledge while maintain a solid base of one’s major field of interest. This crossover can help solve not only the problem of cancer but also many other medical diseases that need cures.

Dongkyu Lee
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Photo by Bomin Park