The temptation is to use the most advanced technology available. A more effective approach is to first define the specific biological question and then select the simplest possible model that can answer it, thus avoiding premature and unnecessary over-engineering.
Industry partnerships are crucial for more than just funding. Collaborating with pharmaceutical companies provides translation-focused questions that guide the design of advanced cell models, ensuring they are predictive, scalable, and compatible with real-world development workflows.
The push away from animal models is a technical necessity, not just an ethical one. Advanced therapeutics like T-cell engagers and multispecific antibodies depend on human-specific biological pathways. These mechanisms are not accurately reproduced in animal models, rendering them ineffective for testing these new drug classes.
Traditional 2D cell cultures can be misleading. Advanced 3D models, by reconstituting the tumor microenvironment with stromal cells, can uncover mechanisms of drug resistance (e.g., to ADCs) that are completely invisible in simpler systems, providing more clinically relevant data.
Scaling from a T-flask to a bioreactor isn't just increasing volume; it's a fundamental shift in the biological context. Changes in cell density, mass transfer, and mechanical stress rewire cell signaling. Therefore, understanding and respecting the cell's biology must be the primary design input for successful scale-up.
CZI's virtual cell models act as a computational "model organism," enabling scientists to run high-risk experiments in silico. This approach dramatically lowers the cost and time required to test novel ideas, encouraging more ambitious research that might otherwise be prohibitive.
A 3D model is considered "advanced" when it's a bioactive system recreating a tissue's microenvironment. It's not just about three-dimensional growth; cells must both influence and be influenced by their surroundings, including architecture, diffusion gradients, and mechanical cues, to be truly representative.
Gene therapy companies, which are inherently technology-heavy, risk becoming too focused on their platform. The ultimate stakeholder is the patient, who is indifferent to whether a cure comes from gene editing, a small molecule, or an antibody. The key is solving the disease, not forcing a specific technological solution onto every problem.
All therapeutic discoveries fall into two types. The first is a biological insight, where the challenge is to find a way to drug it. The second is a technical advancement, like a new platform technology, where the challenge is to find the right clinical application for it. This clarifies a startup's core problem.
It's easy to get distracted by the complex capabilities of AI. By starting with a minimalistic version of an AI product (high human control, low agency), teams are forced to define the specific problem they are solving, preventing them from getting lost in the complexities of the solution.
There's no universal bioreactor setting for 3D tissue models. Each tissue type has unique biological needs. For instance, neural cells require minimal shear stress and low oxygen, whereas liver cells need rigorous perfusion flow to maintain metabolic competence, mandating highly tailored process design for each model.