Bioanalytics
Priya Chockalingam, PhD (she/her/hers)
VP, Head of Clinical BioAnalytics & Translational Sciences
Beam Therapeutics
Cambridge, Massachusetts
Karen Quadrini, PhD
Director, Biomarkers and Precision Medicine
Passage Bio, Inc
Philadelphia, Pennsylvania
Gene edited products are heterogeneous, complex, and require thorough characterization. Several elements drive the complexity including cell lineage; hematopoietic stem cells may differentiate into different cell types. Cells transduced with a lentiviral vector may differ in transduction efficiency and the number of copies incorporated into the genome. Cells edited by a gene-editing tool may be variable in on- and off-target editing, as well as other aspects like zygosity, and aberrant translocations. When a therapy requires multiple edits, heterogeneity of edits is expected across the cells, including edit co-occurrence and zygosity.
The rapid development of new cell and gene therapies is outpacing our ability to adequately characterize them & conduct safety assessments. Conventional methods are often expensive, utilizing multiple platforms and instruments that require harmonization of data output, and bulk analytical methods that output averages fail to capture cell-to-cell variation. Availability of cells & patient samples for testing in various platforms in parallel is also a challenge.
Single-cell multimodal data capture resolves the complexity of edit zygosity and co-occurrence, measures on-target and predicted/known off-target effects, identifies indels, SNVs, and translocations, and quantifies copy number with custom assay development. Paired genotype and immunophenotype analyses in vitro and ex vivo for therapy and disease help understand disease clonal architecture and investigate therapeutic resistance by detection of rare clones. Significant efforts are underway to investigate the potential use of Single-cell multi-omics for responses and toxicities after cell and gene therapies.