1 Application of information technology such as AI in biomedicine
The deep application of information technology such as Artificial Intelligence in the field of Biomedicine, namely "Artificial Intelligence + Biomedicine", refers to the enterprises and research institutions through the combination of artificial intelligence and biomedicine to achieve innovative breakthroughs in the field of biomedicine.
In 2020, DeepMind released the AI algorithm AlphaFold 2, which can accurately predict the 3D structure of proteins based on amino acid sequences, and its accuracy is comparable to the 3D structure analyzed by experimental techniques. The achievement is considered to have solved a major challenge in biology for 50 years, triggered a shock in the scientific community, and once again set off a boom in the research and industrialization of "artificial intelligence + biological medicine".
In 2022, Meta's ESMFold, based on the latest geometric deep learning model "EquiBind," successfully predicted the structure of more than 600 million proteins 60 times faster than AlphaFold .
"Ai + biomedicine" has been applied in many subfields of biomedicine (new drug development, enzyme and protein design, medical image analysis, disease prediction, disease prevention, intelligent diagnosis, precision medicine, etc.), and is expected to widely reshape the status quo of biomedical research and industry.
2.Recombinant antibody technology
Recombinant antibody refers to antibodies produced using molecular biology techniques such as recombinant DNA.
The most distinctive feature of recombinant antibodies is that the amino acid or DNA sequence encoding their antibody protein is known. Therefore, when preparing recombinant antibodies, people can insert the gene sequence encoding recombinant antibodies into the expression vector through recombinant DNA and other technologies, and transfer it to the expression host (such as mammalian cells, yeast or bacteria), and then express and purify to obtain a specific type of recombinant antibodies. Different from monoclonal antibodies produced by traditional polyclonal antibody/hybridoma technology, recombinant antibodies have the advantages of non-animal source production and high batch to batch consistency, which can meet the needs of large-scale antibody production, and control the quality stability of antibody production with a standardized production process.
Another significant advantage of recombinant antibodies is that they are easy to engineer.
Recombinant antibodies can be humanized to reduce immunogenicity by means of molecular biology and synthetic biology. Or rearrange or replace the heavy chain, light chain or partial fragment region of the recombinant antibody to design the recombinant antibody with new antibody characteristics. Through phage display and other technologies, it is also possible to screen recombinant antibodies with high throughput for antibody performance, so as to quickly screen out those recombinant antibodies that can specifically target specific therapeutic significance. These properties allow recombinant antibodies to be modified into different forms for specific applications.
For example, recombinant antibodies that specifically target histone post-translational modifications not only accelerate and improve epigenetic research, but also promise new research breakthroughs.
3 Small molecule inhibitor technology
小分子药物一直在医学进步中发挥着重要作用，并解决人们未满足的需求，其也是每年新批准药物中占比最大的药物类型（2022年FDA批准的新药中，小分子药物占比超过五成[2]）。
截至2022年8月5-11日，美国FDA批准用于肿瘤适应症的小分子抑制剂有88种，首次发表：2022年10月13 资料来源：https://doi.org/10.1002/mco2.181
By August 5 to 11, 2022, the FDA approved for cancer indications of small molecule inhibitors has 88 kinds, published for the first time: 13 October 2022 source: https://doi.org/10.1002/mco2.181
Small molecule inhibitor (Small molecule inhibitor) belongs to the small subclass of drugs, refers to a class of organic compound molecules with molecular weight less than 1000 Dalton that can target proteins, reduce protein activity or hinder biochemical reactions. Small molecule inhibitors reduce the activity of target proteins by directly binding to target proteins, competing with substrates, changing protein structure, or obstructing protein conformational transformation.
Due to the characteristics of small molecular weight, small molecule inhibitors have advantages compared with other types of drugs in terms of good oral absorption, easy penetration of cells, barrier transmission (such as blood-brain barrier), good pharmaceutical performance, and pharmacokinetic properties. These characteristics make small molecule inhibitors gain the favor of the market and new drug development. In recent years, thanks to the development of technologies such as artificial intelligence, computational chemistry, molecular docking, protein structure analysis and prediction, people can explore new targets of small molecule inhibitors more effectively, and carry out rational drug design of small molecule inhibitors, thus accelerating the research and development of new drugs of small molecule inhibitors.
4 High-throughput sequencing technology
High throughput sequencing refers to the sequencing of various biological sequences (such as DNA, RNA, protein, etc.) in a high throughput, fast, efficient, and economical manner.
In the traditional sense, high-throughput sequencing usually refers to the specific high-throughput gene sequencing, the National Development and Reform Commission issued the "14th Five-Year Plan" bioeconomic development Plan proposed: "to speed up the development of high-throughput gene sequencing technology, promote the single-molecule sequencing as a symbol of the new generation of sequencing technology innovation, and constantly improve the efficiency of gene sequencing, reduce sequencing costs."
However, with the emergence of technologies for high-throughput sequencing of non-nucleic acid sequences such as proteins in recent years, the meaning of high-throughput sequencing has also expanded.
5 Drug conjugates technology
Drug conjugate refers to a class of drugs that can be generated using specific linkers (usually chemical chains) to link ligands with effector molecules that have targeting properties. The key idea is that localization ligands can play the role of targeting delivery, and effector molecules can play the role of therapy.
Take the representative antibody drug conjugate (ADC), which has been developed well in recent years, as an example. By using antibody as a localization ligand, the composition of ADC can be expressed as "antibody-link-effector molecule". Compared with traditional drugs, ADC has better targeting of drug delivery.
In recent years, ADC technology has been improving, and the incidence of adverse reactions of improved ADCs has also been significantly reduced. With new ADCs such as Brentuximab vedotin (trade name Adcetris) and Trastuzumab emtansine (trade name Kadcyla) approved by the FDA for the treatment of Hodgkin's lymphoma and HER2-positive breast cancer, ADC drugs have once again entered the field of research.
At present, ADC still has a huge room for development. Advances in technologies such as directed coupling, polyvalent coupling, recombinant antibodies and small molecule drugs have brought new possibilities for the development of ADC drugs, and ADC drugs based on single-chain antibodies, nanoantibodies, bisecial antibodies and other types of antibodies have continued to emerge.
6 Therapeutic gene editing techniques
Therapeutic gene editing refers to a class of therapies that achieve therapeutic effects through targeted editing of genes (knockout, insertion, replacement, modification, etc.).
CRISPR-Cas gene editing technology has the characteristics of wide editing range, easy to use, high efficiency and low cost, and is widely used in life science, drug research and development. In recent years, due to the increasing maturity of this technology, its direct clinical research in therapeutic gene editing has also increased.
7 Cell therapy techniques
Cell therapy is a type of therapy in which living cells are transplanted into a patient to achieve a therapeutic effect. Cell therapy can be further subdivided according to the type of therapeutic cells used, such as cellular immunotherapy based on immune cells, stem cell-based stem cell therapy, etc.
Cellular immunotherapy works by implanting engineered immune cells into the body. In terms of cellular immunotherapy, Chimeric antigen receptor T cell (CAR-T) therapy has made rapid breakthroughs in recent years. The main principle is to introduce the engineered CAR (a synthetic transmembrane receptor) gene into T cells, and then cause T cells to specifically kill tumor cells expressing specific tumor antigens.
In 2017, the first CAR-T therapy (developed by Kymriah) was approved by the FDA for the treatment of acute lymphoblastic leukemia.
In the future, more types of cells will be developed for cell therapy; Personalized, customized cell therapy from the patient is expected to provide new treatment options for more incurable diseases.
