Current large molecule capabilities include detection of oligo, peptide, or antibody therapeuticsusing standard ELISA or MSD-ECL ligand-binding platforms.A variety of formats are available including but not limited to direct, indirect, sandwich, competitive, and multiplex which can be performed with off-the-shelf assays or developed in-house.  For oligonucleotide detection by hybridization, CMIC Inc. brings a wealth of experience with capture and detection probe-based assays for quantitation of antisense or siRNA based therapies.

CMIC Inc.’s flow cytometer has the ability to detect up to 13 colors, and is equipped with a 96-well plate loader to handle high-throughput applications.  The software is 21 CFR Part 11 compliant, and displays easily viewed data.Immuno-phenotyping on whole blood, PBMC, or bone marrow can be performed with a general panel to determine the percentage of T- and B-cells, Natural Killer, and monocyte/macrophage lineage within the leukocyte population.  Alternatively, specialized panels such as regulatory T-cells (Treg cells) can be characterized.  Treg cells play a role in regulating or suppressing other cells in the immune system, and can be defined by the cellular markers CD25, FoxP3, and CTLA4, and the intracellular cytokines IL4 and TGFβ.  Another specialized type of T-cell (one that is important for battling foreign invaders) is the CD4+ memory T-cell, which can be identified by staining CD45RA and CCR7 to determine the percentage of naïve, central memory, and effector memory T-cells within the overall T-cell population. Other flow cytometry applications include confirmation of gene expression in order to establish potency of gene therapy, or the efficacy of a treatment regimen. 

Real-time qPCR has emerged as a powerful tool for bioanalysis, and offers the ability to explore mRNA gene expression.  RNA can be isolated from whole blood, PBMC, bone marrow, solid tissue, or matrices such as urine, saliva, or cerebrospinal fluid and then added to a reverse-transcriptase quantitative PCR to accurately quantify mRNA levels.  Alternatively, DNA can be isolated and added to a qPCR to identify single nucleotide polymorphisms, for detection of known mutations, or to determine individual copy number variation.One of the more powerful applications of qPCR is the ability to multiplex, which is the detection of many targets within the same reaction.  This can be leveraged for biomarker screening to determine which genes are differentially regulated in response to therapeutic treatment.  CMIC Inc.’s qPCR instruments are compatible with a variety offlourophoresand are fully supported by the vendor, providing for seamless design of specialized panels, thereby saving precious time and cost.Yet another application for qPCR is detection of viral nucleic acids in order to determine the remaining levels of a vaccine or gene therapy vector in order to establish washout and allow further optimization of a dosing regimen.

CMIC Inc. plans to add droplet digital PCR and cell-based assays in 2021 to augment current GLP capabilities for bioanalytical support of gene therapy programs. While industry and regulatory contemporaries are building out a knowledge base for new and updated assays, CMIC Inc. will be well positioned to support large molecule biologics ranging from monoclonal antibodies, biosimilars, anti-cancer compounds, peptide-based therapies, gene therapy, and vaccines.

Jenny Lin
Management
COO
Website
www.cmicgroup.com