In treating conditions like heart failure, Gordian's approach is not to replace damaged cells but to use gene therapy to "reprogram" existing, dysfunctional ones. This strategy aims to restore the normal function of the patient's own tissue rather than engaging in the more complex task of rebuilding it.

Instead of harvesting mature macrophages, Resolution Therapeutics extracts their precursor cells (monocytes). This allows them to control differentiation outside the body with a specific cytokine mix, "phenotype locking" the cells into a desired regenerative state before reintroduction into a patient's highly inflamed liver environment.

Create's strategy is not limited to a single cell type. They view success in solid tumors as requiring the programming of all immune cells. Their platform can specifically engineer myeloid cells, T-cells, and NK cells in vivo, orchestrating a coordinated, multi-pronged attack on cancer.

Instead of focusing solely on T-cells, Create's platform first targets myeloid cells, which constitute up to 60% of some solid tumors. Programming these cells transforms the tumor microenvironment, enabling a 5-10x influx of CD8 T-cells. This overcomes a key barrier for T-cell therapies in solid tumors.

While personalized cancer vaccines require extracting and processing a patient's tumor, Create Medicines' in vivo approach is entirely off-the-shelf. By delivering the programming directly into the body, they enable the patient's own immune system to do the complex, personalized work of attacking the cancer itself.

While complex gene editing may be challenging in vivo, Colonia's platform presents a novel opportunity: targeting different immune cell types (e.g., T-cells and NK cells) with distinct payloads in a single treatment. This could create synergistic, multi-pronged attacks on tumors, a paradigm distinct from current ex vivo methods which focus on engineering a single cell type.

Despite significant progress in managing symptoms for autoimmune conditions, very few treatments fundamentally alter the disease's course. The major unmet needs and investment opportunities lie in therapies that can induce remission or target common underlying pathologies like fibrosis, moving beyond mere symptom relief.

Create Medicines chose LNP-delivered RNA for its in vivo platform to give physicians control. Unlike permanent lentiviral approaches, repeatable dosing allows for adapting to tumor antigen escape and managing durability and safety over time. This flexibility is a core strategic advantage for complex diseases like solid tumors.

Instead of searching for elusive natural markers to target, EARLI's platform creates its own. It programs synthetic genetic "switches" that activate only inside cancer cells, turning them into factories that produce their own cancer-fighting therapies. This shifts the paradigm from biological discovery to biological engineering.