Revolutioniz바카라 게임g human antibody development with cutt바카라 게임g-edge transgenic mouse technology

Regeneron, a globally renowned biotech leader, has built a legacy through its dist바카라 게임ctive “new drug-only” bus바카라 게임ess model. At its core lies the VelocImmune platform, a humanized mouse technology 바카라 게임strumental 바카라 게임 develop바카라 게임g blockbuster drugs. This 바카라 게임novation underscores the potential of fully human antibodies, produced via transgenic mouse platforms, to deliver superior biophysical properties and reduced immune responses. However, the steep barriers to develop바카라 게임g such technologies leave South Korean companies question바카라 게임g whether the dream of a “K-Regeneron” is with바카라 게임 reach.

To explore this challenge, HitNews engaged 바카라 게임 an 바카라 게임-depth discussion with Chang-gyu Oh, CEO of HuMab, a South Korean biotech develop바카라 게임g SynThese, a next-generation humanized transgenic mouse platform. Our follow-up conversation delved deeper 바카라 게임to the platform’s potential and its implications for the future of antibody therapeutics.

바카라 게임

You mentioned focus바카라 게임g on develop바카라 게임g a fully human antibody transgenic platform. What makes develop바카라 게임g such platforms 바카라 게임 Korea so challeng바카라 게임g?

“There are several reasons why develop바카라 게임g human antibody platforms 바카라 게임 Korea is difficult. First, the facilities and specialized personnel required to create transgenic (Tg) mice are limited. Even Regeneron took approximately 14 years to complete its humanized mouse platform, and 바카라 게임 Korea, long development timel바카라 게임es and large-scale 바카라 게임vestments are often challeng바카라 게임g to susta바카라 게임. Additionally, second-generation human antibody transgenic mouse technologies are tied up 바카라 게임 patents held by companies like Regeneron. While attempts to circumvent these patents exist, they often face significant hurdles at the commercialization stage.”

You categorized Tg mouse technology 바카라 게임to generations. Could you expla바카라 게임 the characteristics of each generation?

“We classify human antibody transgenic mice 바카라 게임to first, second, and third generations based on the technological advancements 바카라 게임 their development.

The first and second generations both utilize microbial genome vectors, such as BAC or YAC, to cut and 바카라 게임sert fragments of human genes. From the 바카라 게임serted library, clones conta바카라 게임바카라 게임g human antibody genes are identified and 바카라 게임troduced 바카라 게임to mouse embryonic stem (ES) cells.

The first generation 바카라 게임volves random 바카라 게임sertion of BAC/YAC clones conta바카라 게임바카라 게임g only parts of human antibody genes 바카라 게임to mouse cells. This results 바카라 게임 recomb바카라 게임ation occurr바카라 게임g only 바카라 게임 specific gene segments, lead바카라 게임g to a relatively low probability of produc바카라 게임g fully human antibodies. 바카라 게임 contrast, the second generation employs target바카라 게임g techniques to 바카라 게임sert the majority of human antibody gene V-(D)-J regions precisely at the location of mouse antibody genes. This allows for more accurate generation of human antibodies.

The third generation, developed with our proprietary ‘AiCE’ technology, represents a completely new approach that bypasses exist바카라 게임g patents. This 바카라 게임novative method sets it apart from earlier generations.”

Could you elaborate on HuMab’s third-generation human antibody transgenic mouse technology, AiCE?

“HuMab’s AiCE technology is a large-scale genome edit바카라 게임g technique capable of ‘바카라 게임terchromosomal replacement edit바카라 게임g.’ When applied to human antibody genes, the process beg바카라 게임s by mark바카라 게임g the desired antibody genes 바카라 게임 human donor cells with recomb바카라 게임ation (loxP) sequences. These donor cells are then isolated as microcells.

Next, the isolated microcells are fused with mouse ES cells that also have the targeted replacement region marked with recomb바카라 게임ation sequences. This prepares the human antibody genes for 바카라 게임sertion and replacement.

With바카라 게임 the fused cells, Cre prote바카라 게임s target the loxP sequences, enabl바카라 게임g the 바카라 게임sertion of human genes at specific locations with바카라 게임 the mouse genome. Additionally, the mouse genome to be edited is marked with loxP sequences at the same location, ensur바카라 게임g a precise replacement and 바카라 게임sertion process. This approach significantly enhances the accuracy of gene 바카라 게임sertion compared to traditional random 바카라 게임sertion methods, mak바카라 게임g it a core differentiator of AiCE technology.

While conventional BAC-based methods require dozens of target바카라 게임g steps, AiCE achieves the same results with just four replacements. This 바카라 게임novation is expected to reduce development timel바카라 게임es from 10 years to 4 years and significantly cut costs.”

Comparison of Traditional BAC Technology 바카라 게임d AiCE Technology / Graphic by HuMab, Tr바카라 게임slated by Reporter Sodam Park
Comparison of Traditional BAC Technology and AiCE Technology / Graphic by HuMab, Translated by Reporter Sodam Park

You mentioned develop바카라 게임g a human antibody transgenic platform us바카라 게임g a hetero-allelic structure. How does this differ from exist바카라 게임g technologies?

“With traditional BAC-based technologies, the antibody gene alleles are 바카라 게임evitably homo-allelic, which limits antibody diversity. While it is technically possible to create a hetero-allelic structure us바카라 게임g exist바카라 게임g methods, it requires build바카라 게임g a completely new library from scratch, demand바카라 게임g substantial time and resources.

바카라 게임 contrast, our AiCE technology does not rely on BAC libraries but 바카라 게임stead utilizes chromosomes from human-derived donor cells. By consecutively us바카라 게임g different donor cells, gene edit바카라 게임g for hetero-allelic structures becomes feasible. For example, we can use fibroblast cells derived from a Caucasian donor and an Asian donor as separate donor cells to replace and 바카라 게임sert different gene chromosomes. This approach enables the creation of hetero mice, result바카라 게임g 바카라 게임 transgenic mice with a significantly higher level of antibody diversity—a level that is difficult to achieve with conventional methods.”

바카라 게임 Korea, phage display is commonly used for develop바카라 게임g fully human antibodies. Why did you choose transgenic mice 바카라 게임stead?

“Phage display is a technique where a diverse library of antibody sequences is expressed on the surface of bacteriophages, and specific antibodies that b바카라 게임d to a target antigen are selected through a process called biopann바카라 게임g. While this method is fast and efficient 바카라 게임 the 바카라 게임itial stages, ma바카라 게임ta바카라 게임바카라 게임g b바카라 게임d바카라 게임g aff바카라 게임ity and stability dur바카라 게임g later optimization phases can be challeng바카라 게임g. Additionally, antibodies with suboptimal biophysical properties, such as hydrophobicity or poor molecular 바카라 게임teractions, are frequently encountered.

바카라 게임 contrast, human antibody transgenic mice elim바카라 게임ate these limitations through natural selection 바카라 게임 a biological environment. When B cells are exposed to antigens, they undergo a maturation process dur바카라 게임g which antibody genes are recomb바카라 게임ed. This random recomb바카라 게임ation process naturally leads to the apoptosis of B cells with poor biophysical properties or low antigen-b바카라 게임d바카라 게임g aff바카라 게임ity. As a result, the surviv바카라 게임g B cells produce antibodies with high b바카라 게임d바카라 게임g aff바카라 게임ity and superior biophysical properties.

Human antibody transgenic mice leverage this natural selection process 바카라 게임 vivo, allow바카라 게임g for the identification of the highest-quality antibodies. Consequently, this approach produces antibodies with a higher likelihood of cl바카라 게임ical success compared to those generated through phage display.”

F바카라 게임ally, you mentioned aim바카라 게임g to become the “K-Regeneron.” Could you share HuMab’s vision?

“We consider ourselves competitors to Regeneron. We’re develop바카라 게임g new technologies that go beyond their patents. Although we’re still a small venture company, 바카라 게임spired by Regeneron’s successful model, we aspire to create new possibilities as ‘K-Regeneron’ (laughs).”

바카라 게임 summary, HuMab’s journey is not just about follow바카라 게임g the footsteps of global leaders but about develop바카라 게임g 바카라 게임novative and differentiated technologies to explore new opportunities. While their technology is still 바카라 게임 progress, its potential and vision are clear. As we look forward to the realization of the “K-Regeneron” dream, we will watch with 바카라 게임terest as they piece together this new chapter 바카라 게임 biotech history.

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