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Therapeutic Antibody-coding mRNA

Background mRNA-Encoded Antibodies Services Highlights FAQs Published Data

Background

Nowadays, different approaches to turning messenger RNA (mRNA) into a potent therapeutic have been developed. All of them share utilization of specifically designed, instead of endogenous sequences and thorough purification protocols. Using our innovative mRNA platform, Creative Biolabs develops mRNA that encodes functional antibodies or antibody fragments. When our mRNA is delivered to the target cell, the cell's machinery recognizes it and translates it, restoring or augmenting protein function to treat diseases. We now provide customized therapeutic antibody-coding mRNA development services for global clients.

  • mRNA: A Novel Avenue to Antibody Therapy

An elegant solution to circumvent the problems of complex production, purification processes and aberrant post-translational modifications of the monoclonal antibody (mAb), is to deliver the genetic information of the antibody itself. Transient gene transfer aims at administering the mAb-encoding nucleotide sequences directly to patients. This allows the in situ production of biologicals in a labor- and cost-effective manner, potentially for a prolonged period of time. Firstly, effective antibodies have to be raised or selected for the target of interest such as protein, toxin, tumor, bacterium or virus. The respective amino acid sequence can then be encoded in an mRNA designed to produce high amounts of protein. Upon in vivo administration, typically using specific formulations for delivery and mRNA protection against degradation, transfected cells produce the encoded protein, which is not limited to antibody format or localization. Depending on its mode of action, the mRNA-encoded protein finally triggers the desired therapeutic effect.

In vivo administration usually needs formulation of mRNA into nanoparticles to protect against degradation by ubiquitous RNases. Among various modified nanoparticles investigated for therapeutic mRNA delivery, lipid nanoparticles (LNPs) appear to be the most advanced and thus are currently used in most instances. Antibody fragments, such as single-chain variable fragments (scFv), heavy-chain-only VH (VHH) domains, or sdAbs have also been developed and mRNA is capable of encoding any of those antibody variants.

  • Advantages of mRNA-Encoded Antibodies

mRNA-mediated antibody expression is applicable to oncology as well as infectious diseases and may provide advantages compared to recombinant biologics in certain instances such as short-lived antibody formats.

  • First, mRNA gives rise to protein expression for typically a few days instead of providing a single protein pulse upon administration.
  • Second, mRNA offers the advantage that individual sequences are much more similar regarding physicochemical characteristics than different antibodies, thereby enabling a generic process that reduces costs.
  • Third, mRNA-mediated antibody expression can address intracellular targets, since nucleic acids can be readily transfected into cells. In contrast, the delivery of proteins through the cell membrane is challenging.

The Pros of mRNA Compared with Recombinant Protein Regarding Passive Immunization

  • Cell-free production
  • Uniform physiochemistry of drug substances
  • The same technology for all antibody formats
  • Potential for storage at ambient temperature
  • mRNA half-life confers improved pharmacokinetics
  • Accessibility of intracellular targets
  • Potentially improved tolerability due to patient-specific antibody modification
  • Opportunity to reduce systemic exposure by in situ synthesis
  • Potential of high antibody titers with low doses of drug substance

mRNA-Encoded Antibodies Services

Our unique platform has enabled us to develop product candidates designed to deliver mRNA that can carry instructions to produce secreted, intracellular and transmembrane proteins. Besides, our platform is designed to be flexible and scalable by allowing for the development of products that vary only in the mRNA sequence and the tissue-specific delivery vehicle. This modular nature of our platform enables us to rapidly advance into new indications after successfully establishing delivery vehicles for specific tissues.

Although studies on mRNA-based antibody expression are still very limited in number, data support the notion that it may develop into a competitive therapeutic approach. Creative Biolabs believes that our mRNA design, delivery and manufacturing capabilities provide us with the most advanced platform for developing product candidates that deliver mRNA encoding functional antibodies. If you are interested in our services, please feel free to contact us for more information.

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Highlights

  • Innovative mRNA-Based Antibody Development: Creative Biolabs specializes in developing mRNA that encodes functional antibodies or antibody fragments, offering a novel and efficient approach to treating diseases by restoring or augmenting protein function directly within target cells.
  • Cost-Effective Antibody Production: Our mRNA platform circumvents the complexities of traditional antibody production by delivering genetic information directly, enabling in situ protein synthesis, reducing labor, and lowering overall costs.
  • Versatile Antibody Encoding Capabilities: Our mRNA technology can encode various antibody formats, including single-chain variable fragments (scFv) and heavy-chain-only VH domains, allowing for flexible and customized therapeutic solutions.
  • Modular and Scalable mRNA Platform: Our flexible and scalable mRNA platform allows for rapid adaptation to new therapeutic targets by simply altering the mRNA sequence and delivery vehicle, enabling swift progress in diverse medical indications.
  • Expertise in mRNA Design and Manufacturing: Creative Biolabs leverages its advanced mRNA design, delivery, and manufacturing capabilities to develop cutting-edge therapeutic candidates, positioning itself as a leader in mRNA-encoded antibody development.

FAQs

Q: What is therapeutic antibody-coding mRNA and how does it work?

A: Therapeutic antibody-coding mRNA is a novel approach where mRNA encodes specific antibodies or antibody fragments. When delivered into target cells, the mRNA is translated by the cell's machinery into functional antibodies, which can then target diseases like cancer or infections. This method allows in situ production of antibodies, offering a cost-effective and flexible alternative to traditional monoclonal antibody therapies.

Q: What are the advantages of mRNA-encoded antibodies over traditional antibody therapies?

A: mRNA-encoded antibodies provide several advantages, including cell-free production, reduced complexity in manufacturing, and the ability to address intracellular targets. This approach also allows for uniform physiochemistry, potential ambient storage, and improved pharmacokinetics, making it a highly adaptable and efficient therapeutic option compared to traditional protein-based antibodies.

Q: How does Creative Biolabs' platform support mRNA-based antibody therapies?

A: Creative Biolabs offers a flexible and scalable platform for developing mRNA-based antibody therapies. This platform supports the delivery of mRNA that encodes various types of proteins, including secreted, intracellular, and transmembrane proteins. It allows rapid advancement into new therapeutic areas by customizing mRNA sequences and delivery vehicles for specific tissues, thus broadening the potential applications of these therapies.

Q: Can mRNA-based therapies target both intracellular and extracellular proteins?

A: Yes, one of the significant benefits of mRNA-based therapies is their ability to target intracellular proteins, which is often challenging with traditional antibodies. By delivering the mRNA directly into cells, these therapies can encode proteins that function within the cell, expanding the range of treatable conditions beyond those accessible to conventional extracellular antibodies.

Q: What types of antibody formats can be encoded by mRNA?

A: mRNA can encode various antibody formats, including full-length antibodies, single-chain variable fragments (scFv), heavy-chain-only VH domains, and single-domain antibodies (sdAbs). This versatility allows for the development of tailored therapies that can address specific targets and mechanisms of action, making mRNA a powerful tool in antibody-based treatments.

Q: What challenges exist in developing mRNA-based antibody therapies?

A: Challenges include optimizing mRNA stability, ensuring efficient delivery, and minimizing immune responses to the mRNA. Creative Biolabs addresses these challenges by using advanced mRNA design and delivery technologies, ensuring that the therapies are safe, effective, and capable of sustained protein expression in target tissues.

Q: How can researchers and developers benefit from Creative Biolabs' services in mRNA-based antibody development?

A: Researchers and developers can benefit from Creative Biolabs' expertise in mRNA design, delivery, and manufacturing. We offers customized development services that enable the creation of therapeutic antibodies tailored to specific needs, supported by a platform that facilitates rapid advancement into clinical applications.

Published Data

The study explored the use of RNA-encoded bispecific antibodies (bsAbs) as a novel therapeutic approach for cancer treatment. Bispecific antibodies are designed to engage T cells and direct them to target and kill cancer cells by recognizing two different antigens simultaneously—one on T cells and one on cancer cells. The experimental results demonstrated that mRNA encoding these bispecific antibodies (termed RiboMABs) could be delivered into mice, where it directed the in vivo production of the bsAbs. These RiboMABs successfully recruited T cells to tumor cells, leading to effective tumor cell lysis and complete elimination of established tumors in mouse models. This approach bypasses the manufacturing challenges and short half-life associated with traditional bsAbs, offering a faster, more durable, and potentially more effective cancer immunotherapy.

Graph showing sustained bi-(scFv)2 protein levels and tumor elimination in mice treated with picomolar bsAb-encoding mRNA. Fig.1 The bsAb-encoding in vitro-transcribed mRNA can eliminate xenograft tumors in mouse models.1

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Reference

  1. Stadler, Christiane R., et al. "Elimination of large tumors in mice by mRNA-encoded bispecific antibodies." Nature medicine 23.7 (2017): 815-817.
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