Inverting the drug discovery funnel: Multiplex in vivo engineering of biologics using a novel technology mCodes

The discovery and development of biologics have witnessed significant methodological innovations, particularly in generating testable candidates in vitro. Yet, the translation of these candidates to in vivo models remains a critical bottleneck. This challenge stems from the reliance on in vitro data, which often poorly predicts in vivo performance, leading to suboptimal selection of molecules for in vivo phenotypic assessments.
Addressing this gap, Manifold has introduced mCodes, an advanced in vivo protein barcoding technology. mCodes enables the simultaneous evaluation and quantification of hundreds of biologic molecules in a single mouse. This technology allows for direct measurement of molecule kinetics across multiple tissues, facilitating the integration of valuable in vivo data early in the discovery and selection process.
Utilizing mCodes, we have successfully identified several biologics with promising properties, such as blood-brain barrier penetration and enhanced brain uptake. These properties are notably difficult to engineer in vitro. When combined with AI-assisted protein engineering, our approach heralds a transformative shift in biologic drug discovery, offering more efficient and predictive in vivo phenotype engineering.