ʎPEXTM Technology Suite
The ʎPEXTM technology suite is developed to accelerate the discovery and production of monoclonal antibodies (‘mAb’). It comprises of a highly miniaturized tissue culture arrays (‘ʎPEXTM Nanoarrays’) that enables large scale screening and single cell cloning of antibody producing B-cells, a proprietary mAb cell line technology called BREATHTM CHO that enables gene editing-assisted gene swapping of the candidate antibody genes with endogenous versions to generate a high mAb productivity cell line, and a gene editing-based technology to activate endogenous genes in antibody production cell lines to increase mAb production.
We have used silicon wafer technology to miniaturize the tissue culture wells by over 100,000-fold such that the same surface area that occupies a conventional 96-wells plate can now accommodate up to 4 million tiny culture wells of less than 1 nanoliter (10-9 L) each. This ‘nanowells’ array enables single cell screening and single cell cloning of up to 106 to 107 cells per plate, allowing for screening of mAb secreting cells (B-cells, CHO transfected cells, etc.) at a scale not previously achievable. Expression of mAbs from single cell clones seeded in the nanowells can be detected within a day of seeding, thus enabling rapid screening and recovery of mAb producing cells.
Gene Editing Enabled mAb Production Cell Line Technology
This breakthrough technology allows for rapid creation of mAb production cell lines that secret high amounts of mAb product (i.e. high mAb productivity). The master cell line called ‘BREATHTM CHO’ is engineered using gene editing to activate endogenous master transcription regulatory elements, which in turn enhances the production of mAb from the cell line. The BREATHTM CHO cell line harbors a full length human IgG1 monoclonal antibody and can be replaced (or ‘swapped out’) with the gene encoding another mAb by using site specific CRISPR guided integration. The gene swap results in the creation of a new cell line that produces the new mAb, but with the same high level of productivity as the original master BREATHTM CHO cell line and uses the same manufacturing process.
ʎPEXTM Gene Editing Mediated mAb Production Enhancement
Our research showed that endogenous genes which increase transcription and translation of mAb genes, i.e. endogenous master transcription regulatory elements (‘MTRE’), can be selectively activated using CRISPR. We have developed a molecular method using CRISPR to activate specific MTRE genes in mAb production cell lines such as CHO cells (Chinese Hamster Ovary), to increase antibody production rates. This technology has been applied to increase mAb production from several cell lines, thereby significantly reduced the cost to manufacture mAb.
ʎPEXTM builds upon our original hybridoma-based technology platform, MabIgX®, which allows for rapid fusion and production of mAbs directly from patients’ antibody-producing B-cells.