NEWS
College Features
- Publish Date：2024-06-06
NYCU Ambitiously Plans Global Exosome Research Base: Focused on Advancing Precision Medicine and Treating Pancreatic Cancer
The NYCU is launching a global research center, led by Dr. Ly James Lee and Dr. Chi-Ying F. Huang, to advance precision medicine using exosomes for treating pancreatic cancer, positioning Taiwan as a leader in biomedical innovation. (Photo from Hao-Yun Peng and Zong-Han Lyu / ZDunemployed studio)
By NYCU Elite
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“Exosomes” are the nanovesicles of cell secretion. In the 1980s, it was discovered to serve as a storage mechanism for cellular waste. However, recently, scientists have found out that exosomes actually contain many elements, such as nucleic acid, protein, etc., and are equivalent to a messenger communicating information between cells. They are also biomarkers used for early detection of disease. Exosomes are known for their low immunogenicity, cytotoxicity, and ability to cross physiological barriers, making them the rising star for gene therapy and precision medicine with small-molecule drugs. Countries worldwide have been proactively involved in studying exosomes, and the exosome-related research was awarded the Nobel Prize in Physiology or Medicine in 2013.
In 2017, Dr. Chi-Ying F. Huang, the Professor at the Institute of Biopharmaceutical Science of National Yang Ming University[1] and the current Associate Dean at the College of Pharmaceutical Sciences of National Yang Ming Chiao Tung University (NYCU), was looking for ways to break through the patent threshold of Lipid Nanoparticles (LNP) technology in big pharmaceutical companies and pave a new path for developing and manufacturing mRNA-based nucleic acid drugs and precision medicine in Taiwan. During this time, Dr. Huang serendipitously met Dr. Ly James Lee, the Emeritus Helen C. Kurtz Professor in the Department of Chemical and Biomolecular Engineering at Ohio State University, at a seminar in the U.S. by chance.
Prioritize Unmet Medical Needs
At that time, Dr. Lee and the research team at Ohio State University successfully developed the “Tissue Nano Transfection (TNT)” nanochip technology that could infuse RNA or DNA into cells to modulate cell mechanisms (e.g., inhibiting or stimulating cell growth) by microcurrent. The technology could also stimulate the cells to release functional exosomes for treating disease. Dr. Lee shared a similar academic philosophy with Dr. Huang, who invited Dr. Lee to join the NYCU research team to officially initiate the exosome research program by the “Yushan Scholar Program” of the Ministry of Education in Taiwan.
Also from Taiwan, Dr. Lee believes “Taiwan has strong semiconductor technology. I wish to conduct biochip research in Taiwan continuously. Perhaps this technology may become another world-leading technology in Taiwan in the future.” Dr. Huang mentioned that NYCU is fortunate to have Dr. Lee join their team and work on exosome research. However, this program is relatively challenging since everything is new to them. Dr. Huang also says, “From the equipment and consumables to personnel training, we all start from scratch. Dr. Lee even privately sponsored partial research funds for this program!”
In 2017, Dr. Chi-Ying F. Huang, the Professor at the Institute of Biopharmaceutical Science of National Yang Ming University[1] and the current Associate Dean at the College of Pharmaceutical Sciences of National Yang Ming Chiao Tung University (NYCU), was looking for ways to break through the patent threshold of Lipid Nanoparticles (LNP) technology in big pharmaceutical companies and pave a new path for developing and manufacturing mRNA-based nucleic acid drugs and precision medicine in Taiwan. During this time, Dr. Huang serendipitously met Dr. Ly James Lee, the Emeritus Helen C. Kurtz Professor in the Department of Chemical and Biomolecular Engineering at Ohio State University, at a seminar in the U.S. by chance.
Prioritize Unmet Medical Needs
At that time, Dr. Lee and the research team at Ohio State University successfully developed the “Tissue Nano Transfection (TNT)” nanochip technology that could infuse RNA or DNA into cells to modulate cell mechanisms (e.g., inhibiting or stimulating cell growth) by microcurrent. The technology could also stimulate the cells to release functional exosomes for treating disease. Dr. Lee shared a similar academic philosophy with Dr. Huang, who invited Dr. Lee to join the NYCU research team to officially initiate the exosome research program by the “Yushan Scholar Program” of the Ministry of Education in Taiwan.
Also from Taiwan, Dr. Lee believes “Taiwan has strong semiconductor technology. I wish to conduct biochip research in Taiwan continuously. Perhaps this technology may become another world-leading technology in Taiwan in the future.” Dr. Huang mentioned that NYCU is fortunate to have Dr. Lee join their team and work on exosome research. However, this program is relatively challenging since everything is new to them. Dr. Huang also says, “From the equipment and consumables to personnel training, we all start from scratch. Dr. Lee even privately sponsored partial research funds for this program!”
Dr. Chi-Ying F. Huang and Dr. Ly James Lee’s exosome research team in NYCU. (Photo from ZDunemployed studio)
In addition to the great hardships in pioneer work, how to select “the research topic” questions the wisdom of the research team. Dr. Lee indicated, “The direction of our research is based on shared interests between Dr. Huang and me. It was to meet unmet medical needs!” This is why the research team ultimately focused on pancreatic cancer as their research topic since pancreatic cancer has been identified as “the most fatal cancer” in Taiwan due to its low survival rate and the fact that it is more challenging to treat with current target medicine than common cancers such as lung and breast cancer.
Dr. Huang indicates that the second reason for choosing pancreatic cancer was the unity of the Taiwanese pancreatic cancer medical research community. From Keelung Chang Gung Memorial Hospital, Taipei Veterans General Hospital, Chung Shan Medical University, and National Cheng Kung University Hospital to Academia Sinica, every institute is willing to share research resources such as pancreatic cancer cases as clinical samples. With their support, the NYCU research team can seamlessly conduct research on detection, diagnosis, and treatment. Taiwan’s small territory allows for easy team formation and dedicated work, making it a unique niche.
In addition to the great hardships in pioneer work, how to select “the research topic” questions the wisdom of the research team. Dr. Lee indicated, “The direction of our research is based on shared interests between Dr. Huang and me. It was to meet unmet medical needs!” This is why the research team ultimately focused on pancreatic cancer as their research topic since pancreatic cancer has been identified as “the most fatal cancer” in Taiwan due to its low survival rate and the fact that it is more challenging to treat with current target medicine than common cancers such as lung and breast cancer.
Dr. Huang indicates that the second reason for choosing pancreatic cancer was the unity of the Taiwanese pancreatic cancer medical research community. From Keelung Chang Gung Memorial Hospital, Taipei Veterans General Hospital, Chung Shan Medical University, and National Cheng Kung University Hospital to Academia Sinica, every institute is willing to share research resources such as pancreatic cancer cases as clinical samples. With their support, the NYCU research team can seamlessly conduct research on detection, diagnosis, and treatment. Taiwan’s small territory allows for easy team formation and dedicated work, making it a unique niche.
A Tremendous Step Forward for Precision Medicine in Pancreatic Cancer
Dr. Lee analyzes, “The most challenging aspect of cancer treatment is ‘targeting,’ which involves directing drugs to the specific location to attack cancer cells effectively. It is difficult to effectively treat tumors using drug carriers like Lipid Nanoparticles (LNP) because they face challenges in penetrating physiological barriers to reach the tumor. Additionally, there is a risk of immunological rejection response. Virotherapy poses an even greater risk of toxicity. As a result, exosomes may be a better solution for precision treatment.
Therefore, the NYCU exosome research team utilizes the nanotransfection technology developed by Dr. Lee to substantially produce engineered exosomes that carry nucleic acid drugs with high RNA doses. These exosomes have artificially modified targeting proteins and humanized monoclonal antibodies on their surface, which allow the drug to penetrate deeper into pancreatic cancer tissues and precisely attack the cancer cells through dual targeting, effectively suppressing the tumors and prolonging the survival rate of the experimental mice. The research findings were published in Nature Communications in October 2023.
Dr. Lee analyzes, “The most challenging aspect of cancer treatment is ‘targeting,’ which involves directing drugs to the specific location to attack cancer cells effectively. It is difficult to effectively treat tumors using drug carriers like Lipid Nanoparticles (LNP) because they face challenges in penetrating physiological barriers to reach the tumor. Additionally, there is a risk of immunological rejection response. Virotherapy poses an even greater risk of toxicity. As a result, exosomes may be a better solution for precision treatment.
Therefore, the NYCU exosome research team utilizes the nanotransfection technology developed by Dr. Lee to substantially produce engineered exosomes that carry nucleic acid drugs with high RNA doses. These exosomes have artificially modified targeting proteins and humanized monoclonal antibodies on their surface, which allow the drug to penetrate deeper into pancreatic cancer tissues and precisely attack the cancer cells through dual targeting, effectively suppressing the tumors and prolonging the survival rate of the experimental mice. The research findings were published in Nature Communications in October 2023.
![An intercollegiate research team from NYCU and NCKU published the latest strategy for treating ductal adenocarcinoma. Based on animal experiment results, it can effectively inhibit tumor growth and increase survival rates. (Chi-Ling Chiang, et al., 2023)[2]](/userfiles/nycuen/images/20240606114130093.png)
Dr. Lee emphasizes that many chemotherapies for tumors are effective at the beginning but become ineffective after a while because cancer cells will strengthen themselves and become stronger. Ultimately, the chemotherapy dose used in patients increases gradually, or the patient has to switch to chemotherapy with stronger effects but with intolerant side effects. Accordingly, the main task of the NYCU research is to utilize targeting exosomes that carry nucleic acid drugs with high RNA doses to decelerate the growth of cancer cells or even reduce their size. With this approach, cancer cells are less likely to develop drug resistance. The next step involves using low-dose, mild chemotherapy to eliminate the controlled cancer cells. In reality, many complicated disease treatments rely on comprehensive therapy, such as gene therapy with radiotherapy, surgery, and chemotherapy, to minimize the side effects of patients.
After analyzing a large number of clinical cases in Taiwan and the U.S., NYCU’s exosome research team published another research essay in Advanced Science in January 2024. The essay pointed out that the lack of early diagnosis is one of the reasons for the high mortality rate of pancreatic cancer. Using biochips to determine the performance change of two biomarkers, Glypican 1 mRNA and membrane proteins, in exosomes has the potential for early-stage pancreatic ductal adenocarcinoma screening and prognosis evaluation of patients treated with advanced-stage pancreatic cancer chemotherapy.
Industry-Academy Resources Integration and Collaboration
Echoing the original intention of “meeting unmet medical needs,” Dr. Huang and Dr. Lee have proactively advanced to establish NYCU Exosomes Research Base, aiming to expand their research scope from cancer research to broader areas.
“NYCU’s technology platform is well-suited for researching rare diseases, such as Fabry disease and Motor Neuron Disease.” Dr. Huang stated. “Our research on acute respiratory distress syndrome, including pneumonia and pulmonary fibrosis, is ongoing, and we aim to provide the latest treatments if another Covid-like epidemic strikes. Moreover, we are working with the Far Eastern Memorial Hospital to promote exosome-based comprehensive therapy for degenerative arthritis in the elderly.”
Dr. Lee adds, “To meet the demand for precision regenerative medicine for exosomes in the super-aged society, we are also planning to develop an exosome-based nasal spray for treating Alzheimer’s disease. Other applications such as nyctalopia, dry eye, hearing loss due to genetic defects, as well as wound repair or burns treatment will also be the future focus of the exosome center.”
Dr. Huang is optimistic about the future of exosome research in Taiwan. In 2018, Taiwan was ranked 22nd in the world in this field, but by establishing a new research center, Dr. Huang hopes to bring Taiwan into the top 10. This will attract more students and experts to join the NYCU research team and allow the industry to focus on clinical research, ultimately benefiting more patients. Through collaborations between colleges and research institutes, as well as the integration of resources from industry, government, and research, Dr. Huang hopes to build a Global Taiwan team. This team will make Taiwan an important base for world-leading exosome research, development and international networking.
[1] In 2021, National Yang Ming University was merged with National Chiao Tung University to become National Yang Ming Chiao Tung University.
[2] Chiang, C. L., Ma, Y., Hou, Y. C., Pan, J., Chen, S. Y., Chien, M. H., … & Lee, L. J. (2023). Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer. Nature communications, 14(1), 6692. https://doi.org/10.1038/s41467-023-42402-3
[2] Chiang, C. L., Ma, Y., Hou, Y. C., Pan, J., Chen, S. Y., Chien, M. H., … & Lee, L. J. (2023). Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer. Nature communications, 14(1), 6692. https://doi.org/10.1038/s41467-023-42402-3
