CRISPR diagnostics

01Overview and value chain#

Markers EC: IVDR 2017/746 | OECD: Biotech & Health | Regulator: FDA (USA), EMA (EU), NMPA (China)

CRISPR diagnostics use the collateral cleavage of Cas12/Cas13 enzymes to detect nucleic acids at attomolar sensitivity (2 aM) in <30 min, enabling decentralized testing without thermocyclers.

Key directions:

1. SHERLOCK (Cas13 RNA detection): RNA targets via collateral cleavage.
2. DETECTR (Cas12 DNA detection): DNA targets with reporter readout.
3. Isothermal coupling (RPA/LAMP front-end): amplification at constant temperature.
4. Lateral-flow readout (paper-strip output): instrument-free visual result.

Sectoral value chain#

[sample] ──> [extraction] ──> [amplification] ──> [Cas detection]
                                  │
                            (collateral cleavage)
                                  │
                                  ▼
[result] <─── [lateral flow] <────┘

Value chain levels#

Cross-cutting technologies:

• Guide-RNA design (gRNA Design): target-specific guide libraries.
• Reporter chemistry (Reporter Chemistry): fluorescent/colorimetric readouts.
• Microfluidic cartridges (Microfluidics): integrated single-use cartridges.

02US#

The US leads on EUA-grade point-of-care platforms.

point-of-care, emergency use, platform companies#

• Mammoth Biosciences: DETECTR-based platforms.
• Sherlock Biosciences: SHERLOCK CRISPR diagnostics.
• FDA EUA pathway: emergency authorization for rapid tests.

03CN#

China scales manufacturing and domestic NMPA approvals.

scale manufacturing, domestic approval, export#

• Tolo Biotech: CRISPR detection kits.
• BGI: sequencing and assay integration.
• NMPA fast-track: domestic IVD approval.

04EU#

The EU operates under IVDR with notified-body conformity.

IVDR conformity, notified bodies, CE-IVD#

• Qiagen: assay reagents and platforms.
• IVDR 2017/746: in-vitro diagnostic regulation.
• CE-IVD marking: conformity for market access.

05Leading companies and research institutes#

06Tech stack and innovations#

The stack couples amplification, guided cleavage and a simple readout.

1. Isothermal amplification (RPA/LAMP):
   • constant-temperature amplification without thermocyclers.
2. Cas collateral cleavage (Cas12/Cas13):
   • guided cleavage triggers reporter signal.
3. Lateral-flow output (Paper Strip):
   • visual result in <30 min, no instrument.

07Value chains and production pipelines#

Industrial pipeline of a CRISPR IVD (ISO 13485)#

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Sample lysis           │ ───> │ 2. Isothermal amp         │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Reporter cleavage      │ <─── │ 3. Cas/gRNA reaction      │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Lateral-flow readout   │ ───> │ 6. Result reporting       │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Sample lysis

A 200 µL swab is lysed to release nucleic acids within 5 min.

Stage 2: Isothermal amplification

RPA/LAMP amplifies targets at 37–42 °C in 10 min.

Stage 3: Cas/gRNA reaction

Guide RNA directs Cas to the target sequence, detecting down to 10 copies per reaction.

Stage 4: Reporter cleavage

Collateral cleavage activates over 1000 reporter molecules per target.

Stage 5: Lateral-flow readout

A paper strip shows a visual positive/negative line in 5 min.

Stage 6: Result reporting

The result is captured to the patient record at about 0.61 USD per test.