Therapeutic Antibody-coding mRNA

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

Technical Platform

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.

Reference

1. Schlake, T.; et al. mRNA: A novel avenue to antibody therapy? Molecular Therapy. 2019, 27(4): 773-784.