CRISPR screening as a service

01Overview and value chain

Markers: [EC: ATMP Regulation (EC No 1394/2007) | OECD: Bio-Pharmaceuticals | Regulator: FDA (USA), EMA (EU), NMPA (China)]

CRISPR screening as a service is a large B2B/CRO segment: high-throughput functional-genetic screening in mammalian cells to find drug targets and resistance mechanisms. Pooled guide-RNA (sgRNA) libraries target knockout (CRISPR-KO), activation (CRISPRa) or inhibition (CRISPRi) of thousands of genes; delivery is by lentiviral vectors at multiplicity of infection MOI <1; readout is deep sequencing (NGS) with MAGeCK bioinformatics. A whole-genome library is 80,000–120,000 unique sgRNAs (4–6 guides per gene), with ≥ 500 cells per guide of coverage.

Key platforms of CRISPR screening:

1. Pooled libraries (Pooled CRISPR Libraries): thousands of plasmids in one tube — the whole genome per experiment.
2. CRISPRa/CRISPRi: dCas9-VP64 (activation) and dCas9-KRAB (repression) without DNA breaks.
3. Single-cell / Perturb-seq: CRISPR screening + scRNA-seq — an expression profile per perturbation.
4. Arrayed screens (Arrayed): one guide per well — phenotypic readout.

Sectoral value chain

[sgRNA library design] ──> [oligo synthesis + cloning] ──> [lentiviral packaging]
                                                              │
                                                  (transduction, MOI<1)
                                                              │
                                                              ▼
[targets (MAGeCK)] <─── [NGS + bioinformatics] <─── [cell selection/screen]

Value chain levels

Cross-cutting technologies of the sector:

• Pooled libraries (Pooled Libraries): the whole human genome in one experiment.
• Perturb-seq: CRISPR + scRNA-seq — an expression profile per gene perturbation.
• Robotic incubators: Cytomat for pools with ≥ 500 cells/guide coverage.

02US

The US holds the patent and commercial lead in contract CRISPR screening.

Synthego, Revvity/Horizon, FDA IND decisions

• Synthego: high-quality sgRNA synthesis and turnkey cell engineering.
• Horizon Discovery (Revvity): the longest-running provider; CRISPRa/CRISPRi libraries.
• FDA: relies on CRISPR-screening data when assessing IND candidates’ mechanism of action.

03CN

China bets on price and the scale of robotic cell culture.

GenScript, Suzhou clusters, national sgRNA libraries

• GenScript: largest B2B producer of plasmids and lentiviral libraries; screening on primary T-cells.
• Suzhou biopharma clusters: screening at 2–3× lower cost than the US.
• China MOST: national sgRNA libraries for crops and livestock.

04EU

The EU prioritises Perturb-seq, structural biology and target de-risking.

DKFZ/Max Delbrück, Perturb-seq, EMA de-risking

• DKFZ (Germany): oncology screening, AI CRISPR-data analysis; glioblastoma resistance.
• Perturb-seq consortia (DE/FR): rare resistance mechanisms to targeted therapy.
• EMA: mandatory target de-risking on cell panels — steady B2B demand.

05Leading companies and research institutes

06Tech stack and innovations

The stack rests on lentiviral vectors, variant Cas9 enzymes and NGS analytics.

1. Lentiviral vectors (3rd generation):
   • self-inactivating (SIN) HIV-1-based systems for stable sgRNA integration.
2. Variant Cas9 (Modified Cas9):
   • Cas9 (CRISPR-KO), dCas9-KRAB (CRISPRi), dCas9-VP64-p65-RTA (CRISPRa).
3. NGS + bioinformatics:
   • Illumina NovaSeq X Plus + MAGeCK/BAGEL for target ranking and false-positive control.

07Value chains and production pipelines

Industrial pipeline of a B2B CRISPR-screening service

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. crRNA library design   │ ───> │ 2. Synthesis & cloning    │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Transduction MOI=0.3   │ <─── │ 3. Lentiviral production  │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Selection (toxin)      │ ───> │ 6. NGS + MAGeCK report    │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Library design

An sgRNA pool — 4–6 guides per gene, 80,000–120,000 sequences total — designed to the client’s targets.

Stage 2: Synthesis & cloning

On-chip solid-phase oligo synthesis, Gibson Assembly cloning into lentiviral vectors.

Stage 3: Lentiviral production

Production in HEK293T, ultrafiltration concentration, titration (TU/ml).

Stage 4: Transduction

Cell infection (e.g. H1975) at MOI = 0.3 — one integration per cell; puromycin selection.

Stage 5: Selection

Experimental (with inhibitor) and control arms; 14 days; dead cells wash out of the pool.

Stage 6: NGS & bioinformatics

sgRNA-cassette PCR, NGS, MAGeCK ranks genes by enrichment/depletion — a resistance-target report.