An Insilico Medicine platform

A single injection transiently programs T cells to eliminate pathogenic cell populations.

The concept

The chassis

Linear mRNA An open strand with a 5-prime cap and a 3-prime poly-A tail. Exonucleases grip both free ends and cut the strand into fragments, so expression rises and falls quickly and stays above the effective level only briefly. Linear mRNA 5′ cap 3′ poly(A) exonucleases grip both ends expression effective level time short working window
Circular mRNA A covalently closed loop with no free ends. Exonucleases are deflected, ribosomes translate continuously around the circle, and a single dose holds expression above the effective level for far longer. Circular mRNA no free ends protein deflected expression effective level time sustained working window

In-Vivo CAR-T

Direct, in vivo programming of T cells

Conventional Chimeric Antigen Receptor T-cell (CAR-T) therapy is a laborious manufacturing process that engineers and expands patient T-cells ex-vivo. An emerging technology termed as in-vivo CAR-T aims to reprogram T-cells in-vivo via lipid nanoparticle-mediated targeted delivery. As such, it offers an attractive alternative to bypass the otherwise complex manufacturing process. Ultimately, it would shorten treatment timeline and reduce the cost and enable scalable off-the-shelf CAR-T therapy.

Mechanistic cascade

From systemic delivery to target-cell clearance

Generally, the immune response must be potent and durable to eliminate the target, yet temporary enough to limit prolonged immune activity. Each step of in-vivo CAR-T (selective delivery, release, efficient CAR expression, T-cell activation, and target engagement) plays a key role in CAR-T therapy efficacy and hence, may offer opportunities for further optimization.

High-detail six-step in vivo CAR T-cell therapy process
1
Step

Design levers & failure modes

CAR-T applications

Use cases: what a programmable T cell can be pointed at

As the CAR-T could be tailored to recognize a wide variety of antigens, the technology can be adopted/applied to a diverse range of pathologies, from cancer to autoimmune disease.

◎What it targets

Example targets
    ◆Why it matters

    Potential benefits
      ✓Outcome goal

      The engine

      From disease biology to therapeutic design

      · pipeline

        The platform

        Our research

        The announcement

        The first AI toolkit for RNA-encoded longevity therapies.

        PandaClaw · AI bioinformatics
        Unedited capture: PandaClaw compiling a circular-mRNA CAR-T landscape review — 5 min 28 s of reasoning into two sourced reports.
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        Platform content is illustrative and does not represent clinical claims.