Menu

Overview

We will showcase the research and development design, as well as future plans, of our engineered exosome therapy project transitioning from laboratory design to the medical first-line market in Proposed Implementation . Our project focuses on the treatment of rare diseases—MPS II, and the process of promoting drug research and development until market launch requires comprehensive consideration of multiple and complex factors to ensure the effective implementation of the project. We need to know the market demand analysis, clinical trials and drug safety evaluation, and the public's understanding of them.

Market Survey

Market research serves as a crucial tool for understanding market demand. Through questionnaire surveys and expert interviews, we can gain a deeper insight into the public's and the medical community's awareness of MPS II. This aids us in clarifying market demand, optimizing experimental design, and enhancing the precision and practicality of our drugs. Enhancing awareness and understanding of public, patients, and medical professional for rare diseases not only boosts societal attention and support for these patients, but also promotes doctors' acceptance and proper application of novel treatment methods, ultimately accelerating the dissemination and application of treatment plans.

At the beginning of the iGEM project, we conducted preliminary investigations. The survey results show that the majority of respondents have a correct understanding of rare diseases and are concerned about the plight of patients; The research results also indicate that respondents have some understanding of exosome therapy, but express concerns about its safety. During the project, we also conducted research on patients and their families, doctors, pharmaceutical companies, and other relevant groups and institutions, who provided us with valuable guidance and advice.

Please click here for more information

Policy Analysis

Conduct in-depth research on China's policies related to the development of rare disease drugs, including support measures such as tax reductions, research and development funding, and market access. This will help us identify policy benefits, optimize clinical trials, and market conversion pathways.

In recent years, China has implemented many policies related to the research and development of drugs for rare diseases. At the 2023 National Conference on Drug Registration Management and Post Market Supervision, it was stated that the reform of the review and approval system would continue to deepen, with a focus on rare disease drugs. On July 5th, 2023, a press conference was held at the State Council Information Office on "Strengthening Drug Supervision and Effectively Ensuring the Safety of People's Medication". The conference stated that rare disease patients are a group that needs to be given special attention, and rare disease medication is also one of the key tasks of the National Medical Products Administration. Thanks to the deepening of drug review and approval reform by the National Medical Products Administration, the review and approval time limit for rare disease new drugs is currently the shortest among all drug marketing applications, which will further accelerate the marketing of rare disease medication and provide rare disease patients with drugs to treat.

Based on the characteristics of MPS II disease and market demand, we will design a scientifically reasonable clinical trial plan. Emphasize the dual evaluation of safety and efficacy to ensure reliable data support for drugs during clinical trials.

Scientific Research

The research and development of engineered exosomes is the core of the entire project, and it is also the foundation for the transformation of drugs from the laboratory into production and the market. During the iGEM project, we have successfully engineered exosomes that can penetrate the blood-brain barrier model through synthetic biology methods, achieving the key stage goals planned during the competition.

Please click here for more information

In future experimental plans, we will continue to conduct cell experiments and optimize from three aspects.

Through these precise optimization measures, we aim to build an efficient and stable delivery system to ensure accurate and error free delivery of exosomes to the lesion site, bringing more effective therapeutic effects to patients.

Production and Transportation

Firstly, we will establish standardized methods for each step of the manufacturing process, establish production processes that comply with Good Manufacturing Practices (GMP), and ensure drug quality. Secondly, we will adopt modern fermentation tank technology, which is widely used in synthetic biology, for intensive production to increase cell density and exosome production.

Develop detailed transportation and storage plans for exosome drugs based on their unique characteristics. Ensure that drugs are not affected during transportation and storage, maintaining their biological activity and safety. Exosomes are a type of extracellular vesicle, and there are certain problems with the freezing and freeze-drying methods currently used for their storage, which require further research and screening. Exosome drugs should be transported to designated hospitals for refrigeration through a low-temperature sealed, real-time monitored cold chain.

Ultimately, we aim to achieve a production, storage, transportation, and sales pattern of centralized production of exosome drugs in factories, freeze-drying and sealed storage, direct cold chain transportation, and injection into designated hospitals, ensuring the maintenance of drug quality.

Application and Regulations

In promoting the clinical application and translation of exosome research, we must uphold a scientific and rigorous attitude, and comprehensively consider multiple complex factors. In December 2018, “ the Expert Consensus on Extracellular vesicle Research, Transformation, and Clinical Applications ” was officially published online in the Journal of Translational Medicine. This consensus aims to promote the integration of industry academia research on extracellular vesicles both domestically and internationally, facilitate the establishment of relevant standards and regulations, rationally guide technological transformation, and serve people's livelihoods. Moreover, it is crucial to comply with a series of laws and regulations for our engineered exosome therapy to become a legitimate clinical treatment. We need to ensure that the treatment methods comply with the provisions of the Drug Administration Law of the People's Republic of China and the Regulations on the Supervision and Administration of Medical Devices. Before conducting clinical trials, we must submit a clinical trial application to the National Medical Products Administration (NMPA) of China and obtain approval. During the clinical trial process, we must comply with the requirements of the "Regulations on Quality Management of Drug Clinical Trials" and the "Regulations on Quality Management of Medical Device Clinical Trials" to ensure the authenticity, reliability, and integrity of the data. We will continue to monitor and promote the in-depth development of exosome research, while also promoting the establishment of relevant standards and regulations, laying a solid foundation for the healthy development of the industry.

Safety

Safety testing runs through the entire experiment, and corresponding safety testing is required at all stages of cell model experiments, animal model experiments, and clinical experiments. In future preclinical trials, we should pay attention to the following safety assessments:

（1）Preliminary assessment: Conduct in vitro cytotoxicity testing to ensure that there are no toxic side effects such as exosome carriers and TAT.

（2）In vivo safety: Use animal models to monitor the safety of long-term administration, including blood biochemical indicators and histopathological analysis.

（3）Immunogenicity study: Evaluate whether the administration of exosome triggers an immune response. By detecting indicators such as the production of drug-resistant antibodies and the release of cytokines, we ensure that the treatment plan does not activate the immune system during long-term use, avoiding possible immune rejection and ensuring the safety and effectiveness of the treatment.

In clinical trials, for rare diseases with chronic disease characteristics that require long-term treatment, the ICH guidelines should be followed. The number of rare disease patients is small, and safety data can also include data from other non rare disease populations. Due to the limited amount of data accumulated in clinical trials for rare diseases, it is crucial to collect safety data after marketing. A drug surveillance system should be established, and a post marketing risk analysis and management plan (RMP) should be improved based on product and disease characteristics before marketing. RMP should be strictly implemented and continuously improved after marketing.

Conclusion and Prospect

Through the implementation of this project, we are expected to successfully transform engineered exosome drugs into effective treatments for rare diseases such as MPS II. We will continue to monitor market trends, policy changes, and technological advancements, continuously optimize and improve project implementation strategies, and provide better treatment options and quality of life for rare disease patients. At the same time, we also look forward to working together with various partners to promote innovative development in the field of rare disease treatment.

• References
  1. 2024 China Rare Disease Industry Trend Observation Report
     Good Clinical Practice (GCP)
     The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guiding Principles for Clinical Research and Development of Rare Disease Drugs
     Expert Consensus on Extracellular vesicle Research, Transformation, and Clinical Applications