Tracking Transcripts in Biologics and Cell Therapies

October, 18, 2022

GEN Interviews Partillion Co-Founder, Prof. Dino Di Carlo on latest advancement in functional single-cell assays and their implications on development of therapies.

Read the original article at Genetic Engineering & Biotechnology News.

The outcomes from biologics and cell therapies hinge on what they secrete. More specifically, protein secretion has important impacts for both the quality and quantity of a therapeutic produced using bioprocessing, says Dino Di Carlo, PhD, the Armond and Elena Hairapetian chair in engineering and medicine at the University of California, Los Angeles.

“For biologics,” he continues, “the rate at which producer cells secrete protein therapeutics—for example, monoclonal antibodies—drives the amount of therapeutic that can be produced per batch and ultimate costs of production; for cell therapies, secreted proteins are a key product attribute that defines a high-quality product.”

A previous GEN story explained how secretion-based screening could improve cell therapies. Here, Di Carlo describes how he and his colleagues used single-cell sequencing information (SEC-seq) to link the secretions and transcriptomes for individual antibody-secreting cells.

The key finding from this work, Di Carlo says, is that “gene transcripts are not necessarily correlated to secreted proteins, which makes the community rethink genetic modification approaches that just focus on overexpressing the gene for the target-secreted protein to achieve an improved therapeutic effect.” For example, the SEC-seq study showed that the levels of mRNA transcripts for immunoglobulin G (IgG) proteins did not correlate with the amount of assembled and secreted IgG—heavy and light chain—in human plasma cells.

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