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Application of Rabbit Breast Animal Reactor in Biopharmaceuticals

2023/08/25

Genetically modified organism reactor (GMOB) refers to a living system that uses genetic engineering technology to convert foreign genes into receptors for efficient expression, so as to obtain expression products with important application value, including transgenic animals, transgenic plants and transgenic microorganisms.

"Reactor" indicates that it is a directional production system, a device that is purpose-built and modified in order to obtain a certain product, but for GMO reactors, this device is a living system with self-organization, self-replication, self-regulation, and adaptive ability. Thus, the GMO reactor acts like a living fermentation tank capable of self-regulation. Therefore, some people compare it to "molecular farming", a genetically modified plant is a plant bioreactor, and a genetically modified sheep is an animal bioreactor.

The domestic transgenic plant bioreactor is leading the way in biological drugs such as Heyuan Biotechnology, whose plant-derived recombinant human serum albumin has entered clinical phase II, and the pre-IPO round has been subscribed by Betta Pharmaceuticals (300558.SZ), and the post-investment valuation has reached 50 billion.

Since the successful construction of the world's first transgenic animal (mouse) in 1980, transgenic technology has made major breakthroughs in more than 30 years, successively obtaining transgenic rabbits, goats, sheep, pigs, cattle, fish and poultry, which has greatly accelerated the progress of animal breeding and improvement. One of the most attractive prospects for genetically modified animals is to act as a bioreactor to produce bioactive protein drugs that humans need, but are difficult to obtain. After Gordon et al. first reported the successful expression and extraction of human medical protein-tPA in the mammary glands of mice in 1987, so far, there are companies in the world represented by France's LFB (which acquired GTC of the United States), Pharming of the Netherlands (with a market value of $61.<> billion) and Alexion in the United States that use transgenic animal reactors to produce precious medical protein drugs.

The recombinant human antithrombin III (ATryn), an antithrombotic drug developed from genetically modified goat milk produced by LFB in France, was approved by the European Union and the US Food and Drug Administration (FDA) in 2006 and 2009 respectively. In October 2010, a human recombinant C10 esterase inhibitor (Ruconest) purified from transgenic rabbit milk produced by Pharming in the Netherlands was approved for production by the European Medicines Agency (EMA) and FDA approval in 1, and the product has been approved for marketing in more than 2014 countries around the world. In 40, the FDA approved a product from genetically modified chickens, Kanuma, to be developed by Alexion, which was acquired by AstraZeneca for $2015.394 billion. In 2020, France's LFB company's recombinant coagulation factor VIIa analogue, Sevenfact, was approved by the FDA for marketing from the milk of genetically engineered rabbits.

From the GMO reactor biologics that have been marketed, we can see that one product comes from poultry bioreactors and three products come from breast bioreactors. The reason why breast bioreactors are the most widely used and successful is that breast bioreactors have three unique advantages:

1) The target product of breast secretion is restricted to the mammary gland, does not enter the body fluid, hardly affects the normal physiological activities of transgenic animals, and there is no situation that the embryos of transgenic animals are lethal or do not grow large;

2) The protein components in milk are mainly casein, whey protein and lactoglobulin, and the target product can be obtained by conventional methods;

3) The mammary gland can carry out a series of post-translational modifications to the expressed target product, so that the target product has similar or even the same biological activity as the natural product, which is naturally suitable for post-translational modification of complex protein drugs.

Among the three approved mammary bioreactor source products, two are from transgenic rabbit mammary bioreactor, one is transgenic goat mammary reactor, compared with goats, New Zealand white rabbit breed breeding cycle is short, its litter number is more, in a short time can obtain the correct construction of transgenic production rabbits, and the production scale conditions are a relatively easy to control process, and not too much hardware affected, because New Zealand white rabbits can be raised in SPF animal houses, As a carrier for the production of transgenic drugs, it can be easily produced in GMP factories, and has the advantages of short incubation cycle, good efficiency, strong safety, low cost and individual uniformity.

Chengdu Biotech Co., Ltd. was established in June 2021, landing in Tianfu International Bio City, High-tech Zone, as the first domestic enterprise to use precision gene editing technology to build an internationally leading new rabbit breast bioreactor platform, the main business is the research and development and production of complex recombinant protein products, including human recombinant protein drugs, antibody drugs, peptide drugs and preparations, recombinant subunit protein vaccines, medical beauty and food additives. BIAOJING undertakes the parent company's technology and know-how, has perfect and strong patent protection and technical barriers, and applies two major gene editing technologies, CRISPR and TARGATT, to reproduce and establish the TARGATT-rabbit mammary bioreactor platform in China. Compared with the existing and widely used animal cells, plant cell reactors and microbial fermentation, the platform has the characteristics of low investment, low cost, high yield (high gene expression level), excellent quality (protein post-modification close to the natural state), simple operation and management of production system, easy change of production scale, strong genetic stability of breeding rabbits, etc., and has a variety of advantages for small scientific research drug development, large to pilot to large-scale production. In March 6, Bio completed a seed round of financing wholly owned by New Value Capital, and a new round of financing is currently underway.

At present, although there are no transgenic plant and animal-derived drugs on the market in China, Heyuan Biotech's transgenic plant products have entered clinical phase II, and Pharming's Ruconest's Chinese commercialization rights have been licensed to Shanghai Pharmaceutical Industry Research Institute, according to the new Value investment research teamIn view of the fact that Heyuan Biotech's genetically modified plant products have been approved for clinical practice, and Shanghai Institute of Pharmaceutical Industry has introduced Pharming genetically modified rabbit product rights, there is no big problem in the policy declaration of Biaojing's products in the future. As a platform company, BIAOJIN has obtained technical recognition from two well-known companies in the early stage of its establishment and reached cooperation intentions, so we look forward to the team of Biotech in the field of transgenic rabbit mammary bioreactor pharmaceutical!

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