By Christian Cobaugh, CEO and Founder
Monoclonal antibodies (mAbs) have emerged as one of the most successful drug products and biochemical reagents of the 21st century, owing to their broad range of activities, target specificity, and ease of manufacturing. There are now several successful platforms available to discover and engineer novel antibodies with desirable drug-like and reagent-quality properties. Some of these platforms use immune-biased repertoires, which involve immunizing lab animals with antigens of therapeutic interest. These libraries are then screened for antibody clones with disease-modifying properties. Reagent antibodies are also widely used in various research technologies, including detection, quantification, and purification platforms, due to their high target-affinity, specificity, and stability. These reagent antibodies are isolated from the sera immunized lab animals, in the case of polyclonal antibodies, or from screening for antibody clones, in the case of monoclonal antibodies.
The immunization process to generate immune-biased repertoires typically involves injecting immunogens, such as purified target proteins, peptides, or cells overexpressing the target on their surfaces, along with immunostimulatory adjuvants. However, manufacturing these antigens or cell lines can be a time-consuming and costly process that requires significant amounts of trial and error. Lipid nanoparticle (LNP)-formulated mRNA encoding antigens is fast emerging as a effective, faster, and simpler way to create immunogens. Once injected, immune cells such as macrophages and dendritic cells, as well as other antigen-presenting cells, the synthetic mRNA will overexpress the protein antigens from the mRNA as either a secreted or cell-anchored protein, or an MHC-1 peptide, depending on the encoded sequence (1, 2). mRNA-encoded antigens not only offer a faster route from concept to immunization, but they also can present a more relevant glycoform and protein structure to the immune system, leading to higher quality antibodies (3).
Vernal Biosciences has a unified mRNA manufacturing platform that rapidly produces high-purity mRNA for all use cases, including immunogens for antibody discovery. In other words, Vernal can create mRNA encoding whole antigens or a series of target epitopes for any antibody target and then formulate the mRNA into ready-to-immunize LNP formulations using this unified platform. Thanks to the purity levels of our platform technology, the immune system is presented with only the full-length mRNA and the full-length target antigen. Furthermore, we have various LNP formulations that have been confirmed to result in high sera titers from intramuscular injections. Other routes of administration, such as intradermal and subcutaneous, are also proven to create high sera titers and high-quality antibodies using the formulations that Vernal manufactures.
Vernal can formulate various payloads using most lipid types, including ALC-0315, SM-102 and MC3. Contact Vernal for LNP formulation services HERE.
Keywords: mRNA, LNP, Antibody, Therapeutics, mAbs
- Roche, P. A., & Furuta, K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nature reviews. Immunology, 15(4), 203–216. (2015). https://doi.org/10.1038/nri3818
- Lazarus, D., Weinstein-Marom, H., Fishman, S., Yossef, R., Zuri, D., Barnea, E., Admon, A., Margalit, A., & Gross, G. (2015). Efficient peptide recovery from secreted recombinant MHC-I molecules expressed via mRNA transfection. Immunology letters, 165(1), 32–38. https://doi.org/10.1016/j.imlet.2015.03.008
- Van Hoecke, L., Roose, K. How mRNA therapeutics are entering the monoclonal antibody field. J Transl Med 17, 54 (2019). https://doi.org/10.1186/s12967-019-1804-8