THE NNP TRINITY

Program. Predict. Produce.

SHIFTBIO's integrated engine transforms cell-derived nanoparticles into a programmable, pharma-grade delivery platform, NNP.

PROGRAM

NSM Scaffold

We uncovered how proteins are selectively enriched in extracellular vesicles and identified a key sorting motif. NSM is our proprietary transmembrane domains that interact with all three major tetraspanins to drive efficient EV sorting.

A universal engineering scaffold that loads hundreds to thousands of therapeutic cargoes per NNP, with plug-and-play targeting for any organ.

NSM Scaffold

High-Density Loading

Engineered to load hundreds to thousands of therapeutic cargoes per NNP

Multi-Cargo Versatility

Unparalleled compatibility with both proteins and nucleic acids (ASO, siRNA, mRNA)

Plug-and-Play Modularity

Customizing targeting moieties for diverse organ specificity

NSM-Cargo
Variants

►

Structure
Modeling

►

Interface
Descriptors

►

ML Model
Prediction

In silico Structure-Activity Analysis

PREDICT

NNP Design AI™

Predict before you build.
Months, not years.

NSM operates through protein-protein interactions with tetraspanins. This means we can computationally model each Cargo-NSM construct, analyze its tetraspanin interface, and predict engineering success before a single experiment is run.

Standardized biodata across every construct powers a machine learning model that turns structural descriptors into actionable design decisions, dramatically reducing development risk and timeline.

PRODUCE

NNP Manufacturing™

Successfully industrialized.
At commercial scale.

Cell-derived nanoparticles have long promised biological advantage but resisted industrialization. SHIFTBIO solved this with a scalable manufacturing process that delivers GMP-grade NNPs with 100× yield improvement, >95% purity, and batch-to-batch consistency.

Cell
Bank

►

3D
Bioreactor

►

DSP
Purification

►

NNP
Product

Scaled for Commercial Production
SHIFTBIO has successfully industrialized NNP

3D

Bioreactor Ready

>95%

High Purity

100×

Yield Gain

Nat. Comm.

Published 2025

AI-DRIVEN ITERATIVE DESIGN

Program, Predict, Produce

A closed-loop cycle where AI predictions are experimentally validated and results refine next-generation designs.

01NNP Design

NSM scaffold + Cargo loading + Targeting moiety

02NNP Design AI™

In silico prediction before wet-lab

03Scalable Manufacturing

Scale-up + High Purity + Consistency

Validated results feed back to refine next-generation designs

NNP TRINITY · PROGRAM · PREDICT · PRODUCE

The NNPtechnology.

Three linked steps: design the particle, rank candidates in silico and manufacture at scale.

PROGRAM / NSM SCAFFOLD

Plug-and-play
targeting and loading.

NSM (NNP Sorting Motif) is our engineering scaffold. It places targeting moieties on the outer surface and therapeutic cargo in the inner cavity.

NNP membrane with tetraspanins CD9, CD81 and CD63, the NSM scaffold crossing the membrane, a targeting moiety on the outer surface and therapeutic cargo in the inner cavity.

Outer surfaceTargeting moiety

NSM (NNP Sorting Motif)Engineering scaffold

CD81

CD9

CD63

Inner cavityTherapeutic cargo

Outer surface
Targeting moiety
NSM
Engineering scaffold(NNP Sorting Motif)
Inner cavity
Therapeutic cargo
  • Loading mechanism

    NSM engages CD9, CD81 and CD63.

  • Surface and interior

    Targeting outside, cargo inside.

  • Multimodal, high capacity

    Diverse payloads, many copies per particle.

PAYLOAD FLEXIBILITY

One NNP.
Three loading routes.

Surface display and internal loading during biogenesis. Post-isolation loading after purification.

NNP with membrane proteins and peptides displayed on its outer surface.ProteinPeptide

Surface display

Payloads
Protein (membrane), peptide
Loaded
During biogenesis
Via
NSM scaffold
Cutaway NNP with macromolecules loaded in its inner cavity.Macromolecules

Internal loading

Payloads
Macromolecules (intracellular)
Loaded
During biogenesis
Via
NSM scaffold
NNP with oligonucleotide conjugates inserted into its outer membrane.siRNA / ASO

Post-isolation loading

Payloads
siRNA, ASO
Loaded
After purification
Via
Cholesterol anchor

PREDICT / NNP DESIGN AI

From uncertainty
to predictability.

Cargo loading varies wildly. We rank every design in silico to build only the top-ranked candidates.

Traditional approach

Build everything,
test afterwards.

Loading efficiency can only be measured after full synthesis and production.

NNP Design AI

Analyzes NSM contacts and cargo sequences. Continuously improves through real-world assay data.

NNP Design AI approach

Build only the
top-ranked candidates.

Build these first

Designs ranked by predicted loading

AI scores prioritize high-potential candidates. Wet-lab validation confirms performance.

Score first, build less: designed to cut build-and-test cycles, time and cost.

PRODUCE / NNP MANUFACTURING

Built for
consistent production.

Cell-derived nanoparticles have struggled with scale and batch consistency. Our process is built for both.

Upstream 3D bioreactor

  1. 013D bioreactor

Downstream Defined purification sequence

  1. 02Harvest

  2. 03Clarification

  3. 04Concentration

  4. 05Chromatography

  5. 06Buffer exchange

  6. 07Sterile filtration

Cells make the carrier.
Our process makes it reproducible.

TWO DELIVERY PLATFORMS

From engineering to delivery.

Explore I-NNP and B-NNP

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