2026

Evolution Suisse · iDEC 2026

Powerful molecules
need better delivery.

RNA and proteins can perform precise biological tasks. Together they are even more powerful, but their usefulness depends on delivery – if they reach the right cells and become available where they act.

We are engineering protein cages toward carrying RNA and protein together.

  1. Protect the
    cargo.
  2. Reach the
    right cells.
  3. Release it
    inside.

Cargo structures: PDB 5F9R

Explore the idea

The opportunity

Some functions need both.

RNA can encode information or guide a molecular interaction. Proteins can perform the corresponding task. For systems that depend on two components, delivery must bring both to the same cell and the compartment where they act.

CRISPR-Cas system puts it into practice - a guide RNA specifies a target, while a Cas protein acts on it. Carrying the protein and its guide together offers a way to coordinate their delivery.

Separate cargo paths need to converge in the same cell Same cell
Two cargoes, separate pathsBoth must arrive where they can work together.
A closed protein cage carries protein and RNA toward the same cell Same cell
One carrier, shared destinationA strategy for coordinating delivery of both.

That motivates a carrier able to load both - a protein and RNA.

Read the delivery background

Our proposed carrier

Could one protein cage carry both?

Encapsulins are self-assembling protein nanocompartments. Their interior offers a place to engineer cargo recognition; their shell provides a scaffold whose sequence can be changed and tested.

We chose QtEncapsulin, a cage of 240 subunits about 42 nm across. Our design combines its native protein-loading peptide with an engineered RNA-binding element on the inner surface.

For our experimental model, dCas9 carries the protein handle and its guide RNA carries boxB hairpins recognized by λN. Whether these engineered shells assemble and co-encapsulate both cargoes remains to be established.

Explore the cage design
Proposed encapsulin with protein and RNA loading routes A cutaway shows protein and RNA cargo inside QtEncapsulin. Protein loading uses a native cargo-loading peptide; engineered RNA recognition uses lambda N and boxB. Cargo structures are from PDB 5F9R. Protein loading Native CLP handle RNA recognition Engineered λN·boxB QtEncapsulin QtEncapsulin
Protein loading
Native CLP handle
RNA recognition
Engineered λN·boxB
Proposed co-loading design · Cargo structures: PDB 5F9R.

The evolution strategy

Build the handles.
Evolve the shell.

Adding ways to load cargo is the starting point. Our next question is whether evolution can improve capture. We propose continuous mutation of the shell cassette, coupled to growth selection in E. coli.

Here, catalytically inactive dCas9 and its guide repress an antibiotic-resistance gene. Sequestering a component reduces the active repressor and can restore growth, giving capture a selectable consequence.

01SilenceThe dCas9-sgRNA RNP binds inside KanR and transcriptionally represses its expression. Cells grow poorly on kanamycin.
02DiversifyMutaT7 mutates only the encapsulin cassette, generating shell variants during growth in culture.
03Select captureSequestering dCas9, sgRNA or both allows KanR to be transcribed, giving cells harboring optimized encapsulin variants a fitness advantage.

Repeat mutation and selection across generations

Views from the Mechanism walkthrough · Cas9 structure: PDB 5F9R.

Planned evolution strategy. Capturing either component can rescue growth. Independent assays must distinguish single-component capture from true co-encapsulation. Mammalian delivery is a longer-term goal.

See how the selection works

Where we are

From design to
experimental validation.

Engineered shell variants have been constructed, shell expression detected, and MutaT7 activity demonstrated. Cage assembly and co-encapsulation remain unconfirmed; the continuous evolution campaign is planned.

The next steps are to validate assembly, complete the selection circuit, and test cargo loading independently.

Read the results and open questions