Unlike broad delivery systems like LNPs, Sana's Fusagen technology uses a modified viral component as a "logic gate." It is engineered to bind to a specific cell target, which then triggers a conformational change that fuses the payload directly into the cell's cytoplasm. This two-step mechanism aims for higher specificity and lasting effect.

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To overcome the historical issue of oncolytic viruses being sequestered by the liver, Accession re-engineers a human virus so it cannot infect any human cells. Only after this safety step is it re-targeted to infect only cancer cells, ensuring precise delivery and avoiding systemic side effects.

Colonia Therapeutics' CEO argues that lentiviral delivery is ideal for oncology's required long-term persistence, while LNP delivery is better suited for autoimmune indications needing transient, multi-dose responses. This frames them as complementary technologies for different therapeutic "swim lanes" rather than as direct rivals in a zero-sum game.

To overcome on-target, off-tumor toxicity, LabGenius designs antibodies that act like biological computers. These molecules "sample" the density of target receptors on a cell's surface and are engineered to activate and kill only when a specific threshold is met, distinguishing high-expression cancer cells from low-expression healthy cells.

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.

Accession's second product is a bispecific antibody that binds to all cancer cells. While this would be dangerously toxic if delivered systemically, their targeted virus delivery system ensures it is only produced inside the tumor. This strategy makes previously "undruggable" therapeutic concepts viable.

A key innovation in Sana's diabetes cell therapy is overcoming the dual immune response. While knocking out MHC expression hides cells from the adaptive system (T-cells), this triggers an attack from the innate system (NK cells). Sana's solution is to overexpress CD47, effectively creating a "don't kill me" signal for both.

Voyager CEO Al Sandrock explains their AAV capsids are engineered to be so potent at crossing the blood-brain barrier that doses can be an order of magnitude lower than standard. Crucially, the capsids are also designed to *avoid* the liver, directly addressing the toxicity issues that have plagued the field.

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.

Beyond transient RNA, Create has developed a unique retrotransposon based on the human Line-1 element. This technology allows for stable, scarless gene delivery using only RNA, providing an option for durable expression (e.g., for CD19 CAR-T) alongside their transient approaches, creating a highly versatile platform.