Our Goal:

We design methods for viral RNA research explorations which applied to the HIV-1 isolate ARV-2/SF2 viral genome design for RNA replication for nucleic acid integrase inhibitors, RNA vaccine development, and their potential methods for targeted drug development. Our goal was to utilize the env non-coding long chain RRE RNA and Rev proteins in the viral genome of the HIV-1 isolate ARV-2/SF2 viral strain to develop means that could be used for nucleic acid integrase inhibitors and RNA vaccines as well as targeted drugs. We are using the RNA vaccine development, nucleic acid integrase inhibitors, virus-targeted drugs. We will state the business plan from the following aspects.

1. Overview of mRNA

RNA therapy refers to therapy that uses nucleic acids with disease-treating functions to regulate the expression of disease-causing genes from the source. RNA therapies are divided into three categories according to their mechanisms of action: (1) mRNA therapies encoding therapeutic proteins or antigens[1]; (2) small nucleic acid therapies that target nucleic acids to inhibit pathogenic RNA activity or activate gene activity, including antisense Treatments such as oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA), small activating RNA (saRNA)[2]; (3) Nucleic acid aptamers (Aptamers) that target proteins and regulate protein activity therapy[3].

mRNA (messenger RNA) is a type of single-stranded ribonucleic acid, which is transcribed from one strand of DNA as a template, carries genetic information and can guide protein synthesis. There are two main categories of mRNA vaccines, both of which can prevent and treat diseases.

2. Advantages of mRNA in the field of cancer

In the field of tumor immunotherapy, according to Moderna's Science Day report, mRNA technology has the following four advantages: (1) Application opportunities for a large number of products, because mRNA can encode multiple antigen genes and has the ability to form a combined vaccine[4]. (2) The technology has a higher probability of success, and its unique mechanism triggers stronger B cell and T cell immunity[5]. (3) It can enter clinical practice and commercialization faster, because as long as the sequence design of mRNA is completed, most of the processes can be standardized[6]. (4) Personalized treatment can be carried out to achieve precise treatment of tumors[7].

mRNA vaccine principle：

1. Vaccine principle: Most vaccines deliver antigens to the body to spontaneously form a specific immune response. After the immune memory is formed, if the human body is attacked by a pathogen, the acquired immunity responds quickly and eliminates the pathogen and susceptible cells before the pathogen infects other cells on a large scale.

2. mRNA vaccine:mRNA vaccine is a nucleic acid vaccine that injects part of the virus's mRNA fragments into human cells to produce antigens, which then stimulates a specific immune response and forms an immune memory effect.

3. Principle of mRNA vaccine treatment: The principle of mRNA treatment vaccine is to deliver the mRNA encoding the antigen into human cells through different delivery methods, and produce the corresponding antigen protein after translation in the cell, thereby effectively stimulating cellular immunity and humoral immunity.

Marketing Analysis of mRNA:

According to an article on the analysis of the mRNA drug market published by Nature Reviews Drug Discovery, the market size of mRNA products is expected to exceed US$50 billion in 2021. According to the report "mRNA Technology Enters a Period of Rapid Development and Has Broad Future Prospects" published by Southwest Securities, the market size of mRNA technology is expected to reach US$32.6 billion in 2025[8].

According to a 2021 Nature Reviews Drug Discovery article analyzing 31 mRNA companies around the world, 77% of the companies have at least one mRNA preventive vaccine, and 35% of the companies have at least one mRNA therapeutic vaccine. , 55% of companies have at least one mRNA therapeutic drug. Of the 76 preventive vaccines, 22% are used to prevent COVID-19 infection, and 77% are used to prevent other infectious diseases; of the 32 therapeutic vaccines, 21% are related to cancer; of the 72 mRNA therapeutic drugs , oncology drugs account for 13%, rare disease drugs account for 20%, and respiratory disease drugs account for 17%[9].

Strength and Opportunity Analysis of mRNA:

Strength:

1）High security. The mRNA vaccine will undergo a natural degradation process when entering the body, and side effects can be more precisely controlled. There is no risk of integration, induced gene mutation, or exogenous virus infection; It has better water solubility and is easier to make medicine;

2）Strong design. Can present a variety of antigens and deliver them to DC cells in a targeted manner;

Opportunity:

Therapeutic drugs may represent the largest opportunity among mRNA drugs, covering many indications, but it is unclear whether mRNA drugs have clinical advantages over other therapies, and there are also high clinical risks. Long-term opportunities will depend on technological advances in areas such as delivery systems and gene editing.

Summary:

According to the report "MRNA Technology Ushers in a Period of Rapid Development, with Broad Future Prospects", taking mRNA vaccines as an example, its average research and development cycle is 0.8-1.5 years, and the process production and construction cycle is 2-4 years[10]. The overall commercialization process is more traditional Path is 10 times faster. The overall cost is 1/18 of the traditional route. Therefore, the mRNA vaccine is significantly better than other technology-based vaccines in terms of research and development, production time, and capital investment.

The application scenarios of mRNA are not limited to the prevention of infectious diseases, but also have significant advantages in the fields of tumor immunotherapy, protein replacement therapy, and regenerative therapy. The international mRNA giant has deployed a rich R&D pipeline in the field of tumor treatment, including products for melanoma, lymphoma and other tumor types.

1、Data source: Compilation of public information

2、Data source: Compilation of public information

3、Data source: Compilation of public information

4、Data source: Moderna's Science Day report

5、Data source: Moderna's Science Day report

6、Data source: Moderna's Science Day report

7、Data source: Moderna's Science Day report

8、https://mp.weixin.qq.com/s?__biz=MzUxNTM5MDcwMA==&mid=2247545118&idx=2&sn=3b744a2cd08409f5aee0d6ec54836cd0&chksm=f9b51c9dcec2958b577d1c4bb4957494c791c7363d7ef0c255da0e4140da52ea40fe0b1b7ea0&scene=27

9、The analysis of the mRNA drug market published by Nature Reviews Drug Discovery

10、Report from Southwest Securities