Atlas of the Present Atlas · v0.1

As of 12 September 2026

Dossier 09

Synthetic Biology

v1.2-draft · unchecked

1. As of

Date
Version
v1.2-draft
Author / model
Atlas generator
Reviewer
unchecked (Josef)

2. In one sentence

CRISPR is approved as ex-vivo HSCT after myeloablation (CASGEVY), not as a pill; Frangoul NEJM 2021 (CTX001, n=2 early report, E1) shows early clinical editing/HbF measurements — not Phase-3/label; in-vivo LNP-CRISPR (NTLA-2001) exists as Phase-1 interim (Gillmore, n=6) — not as an approved product; synthetic genomes are lab objects; DNA screening is mostly voluntary.

Established now · E1 / E2

3. What works today

CRISPR in the clinic is ex-vivo HSCT

  1. E1

    FDA 2023-12-08: two gene therapies for sickle cell disease from age 12. CASGEVY = first CRISPR product. LYFGENIA = lentiviral, not CRISPR.

    FDA 2023-12-08. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. https://content.govdelivery.com/accounts/USFDA/bulletins/37efce0. As of 2023-12-08. Checked 2026-08-28. Type: Agency notice.
  2. E1

    CASGEVY USPI, as of 07/2026: age 2+ SCD and TDT. BCL11A enhancer RNP. Busulfan myeloablation. Not in-vivo. SCD VF12 29/31 (93.5%); 44/58 infused after mobilization. 100% grade 3/4 neutropenia and thrombocytopenia. Age 2–<5 extrapolated. Off-target §5.4 cannot be ruled out.

    CASGEVY USPI. CASGEVY (exagamglogene autotemcel) Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846. As of Revised 07/2026. Checked 2026-08-28. Type: Prescribing information.
  3. E1

    Frangoul et al. NEJM 2021 (DOI 10.1056/NEJMoa2031054; online 2020-12-05; 384:252–260; NCT03655678 / NCT03745287): first two patients infused with CTX001 (autologous CRISPR-Cas9–edited CD34+ HSPCs targeting BCL11A erythroid enhancer) — Patient 1 TDT (19y), Patient 2 SCD (33y). Healthy-donor preclinical: mean allelic editing ~80±6%; paper: ~80% alleles modified, no evidence of off-target editing; candidate off-target 0 of 223 at ≥0.2% threshold (Fig. 1D text). Product allelic editing: Patient 1 68.9%; Patient 2 mobilization lots 82.6% / 78.7%. Governance/clinical measurement only — no protocols, sequences, gRNAs.

    Frangoul et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. https://doi.org/10.1056/NEJMoa2031054. As of published online 2020-12-05; NEJM 384:252–260 (2021-01-21); NCT03655678 / NCT03745287. Checked 2026-09-11. Type: Paper (NEJM; early clinical report).
  4. E1

    After myeloablation + infusion: durable allelic editing in blood/marrow; transfusion independence (Patient 1 last TDT transfusion day 30); Patient 2 no vaso-occlusive episodes during reported follow-up (16.6 months). Patient 1 HbF 0.3→8.4 g/dL mo3 →12.4 mo12 →13.1 mo18; F-cells 10.1%→99.7% mo6. Constrained: still ex-vivo HSCT + busulfan myeloablation (not an outpatient pill); n=2 early report ≠ Phase-3 / label approval (CASGEVY label remains separate E1 for approval).

    Frangoul et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. https://doi.org/10.1056/NEJMoa2031054. As of published online 2020-12-05; NEJM 384:252–260 (2021-01-21); NCT03655678 / NCT03745287. Checked 2026-09-11. Type: Paper (NEJM; early clinical report).
  5. E1

    Gillmore et al. NEJM 2021 (NTLA-2001, NCT04601051): Phase-1 interim, n=6 hereditary ATTR polyneuropathy; single IV total-RNA dose 0.1 or 0.3 mg/kg (3 each). Day-28 mean serum TTR reduction 52% (47–56) and 87% (80–96). Few AEs, mild (grade 1) in 3/6; no SAEs in this report. In-vivo LNP mRNA-Cas9 + sgRNA targeting TTR — proof of concept, ongoing escalation, limited follow-up. E1 for interim measurement; not an approval.

    Gillmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. https://doi.org/10.1056/NEJMoa2107454. As of 2021-08-05 (online 2021-06-26); NCT04601051. Checked 2026-09-04. Type: Paper (NEJM; UCL Discovery OA PDF).
  6. E1

    LYFGENIA PI, 12/2023: LVV, not CRISPR. Boxed warning hematologic malignancy. VOE-CR 28/32.

    LYFGENIA PI. LYFGENIA (lovotibeglogene autotemcel) Prescribing Information. https://www.genetixbiotx.com/-/media/bluebirdbio/Corporate%20COM/Files/Lyfgenia/LYFGENIA_Prescribing_Information.pdf. As of Revised 12/2023. Checked 2026-08-28. Type: Prescribing information.

Synthetic genomes as lab objects

  1. E1

    syn1.0 (2010) exists: a chemically synthesized Mycoplasma genome controls a cell (JCVI page + Gibson abstract). Science full text not opened.

    JCVI syn1.0. First Self-Replicating Synthetic Bacterial Cell. https://www.jcvi.org/research/first-self-replicating-synthetic-bacterial-cell. As of 2010 (page). Checked 2026-08-28. Type: Institute page.Gibson abstract. Creation of a bacterial cell controlled by a chemically synthesized genome (abstract). https://www.jcvi.org/publications/creation-bacterial-cell-controlled-chemically-synthesized-genome. As of 2010. Checked 2026-08-28. Type: Abstract.
  2. E1

    syn3.0: 473 genes, 149 of unknown function. First design not viable (JCVI + Hutchison abstract). Minimal cell ≠ understanding.

    JCVI syn3.0. First Minimal Synthetic Bacterial Cell designed and constructed by scientists at the Venter Institute. https://www.jcvi.org/media-center/first-minimal-synthetic-bacterial-cell-designed-and-constructed-scientists-venter. As of 2016 (page). Checked 2026-08-28. Type: Institute page.Hutchison abstract. Design and synthesis of a minimal bacterial genome (abstract). https://www.jcvi.org/publications/design-and-synthesis-minimal-bacterial-genome. As of 2016. Checked 2026-08-28. Type: Abstract.
  3. E1

    synXVI 903 kb: systematic loxPsym UTR bugs. Sc2.0 whole genome as one living cell not shown in this log.

    Goold synXVI. Construction and iterative redesign of synXVI a 903 021 bp synthetic Saccharomyces cerevisiae chromosome. https://www.nature.com/articles/s41467-024-55318-3. As of 2025. Checked 2026-08-28. Type: Paper (Nature Communications).

DNA screening is practice, not a universal law

  1. E1

    IGSC Harmonized Screening Protocol v3.1 (2026-06-01): no country requires providers to screen. Threshold ≥200 bp now; 50 bp from 2026-10-24.

    IGSC v3.1. Harmonized Screening Protocol Version 3.1. https://genesynthesisconsortium.org/wp-content/uploads/IGSC-Harmonized-Screening-Protocol-V3.1.pdf. As of 2026-06-01. Checked 2026-08-28. Type: Industry protocol.
  2. E2

    OSTP framework is a US federal-funding condition. Page says it will be revised/replaced after EO 14292 and is not yet updated as of 2026-08-28.

    OSTP Framework. 2024 OSTP Framework for Nucleic Acid Synthesis Screening. https://aspr.hhs.gov/S3/Pages/OSTP-Framework-for-Nucleic-Acid-Synthesis-Screening.aspx. As of page as of 2026-08-28. Checked 2026-08-28. Type: US framework (HTML).ASPR Screening. Synthetic Nucleic Acid Screening. https://aspr.hhs.gov/S3/Pages/Synthetic-Nucleic-Acid-Screening.aspx. As of page as of 2026-08-28. Checked 2026-08-28. Type: Agency page.EO 14292. Executive Order 14292, Improving the Safety and Security of Biological Research. https://www.whitehouse.gov/presidential-actions/2025/05/improving-the-safety-and-security-of-biological-research/. As of 2025-05-05. Checked 2026-08-28. Type: Executive Order.

Claimed · E3

4. What is claimed, not shown

In-vivo CRISPR, HHS, JCVI prose

  1. E3

    Vendor/press framing of “in-vivo CRISPR therapy” beyond the Phase-1 interim: Gillmore body is opened (source 16, E1 for n=6/day-28), but approval, long-term benefit and patient off-target rate remain E0/E3 here — not inferred from the interim.

    Gillmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. https://doi.org/10.1056/NEJMoa2107454. As of 2021-08-05 (online 2021-06-26); NCT04601051. Checked 2026-09-04. Type: Paper (NEJM; UCL Discovery OA PDF).
  2. E2

    HHS press release 2026-07-28 on stopping high-risk research: press text opened, full policy not. E2/E3 for the press claim.

    HHS 2026-07-28. Trump Administration Releases New Government-Wide Policy to End Dangerous High-Risk Research. https://www.hhs.gov/press-room/stopping-high-risk-life-sciences-research.html. As of 2026-07-28. Checked 2026-08-28. Type: Press release.
  3. E3

    JCVI 2010 “new era” prose is institute rhetoric, not a measurement.

    JCVI syn1.0. First Self-Replicating Synthetic Bacterial Cell. https://www.jcvi.org/research/first-self-replicating-synthetic-bacterial-cell. As of 2010 (page). Checked 2026-08-28. Type: Institute page.

Constrained · Limit

5. Bottleneck and limit

What clinic and screening are not

  1. E1

    CRISPR ≠ outpatient pill. CASGEVY and Frangoul CTX001 need mobilization, myeloablation, infusion, inpatient neutropenia. Off-target cannot be ruled out (label); early report n=2 ≠ approval.

    CASGEVY USPI. CASGEVY (exagamglogene autotemcel) Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846. As of Revised 07/2026. Checked 2026-08-28. Type: Prescribing information.Frangoul et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. https://doi.org/10.1056/NEJMoa2031054. As of published online 2020-12-05; NEJM 384:252–260 (2021-01-21); NCT03655678 / NCT03745287. Checked 2026-09-11. Type: Paper (NEJM; early clinical report).
  2. E1

    In-vivo ≠ approved: NTLA-2001 is Phase-1 interim (Gillmore 2021); CASGEVY remains the opened approved CRISPR product and is ex-vivo HSCT. No claim that “in-vivo CRISPR is approved” from this log.

    Gillmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. https://doi.org/10.1056/NEJMoa2107454. As of 2021-08-05 (online 2021-06-26); NCT04601051. Checked 2026-09-04. Type: Paper (NEJM; UCL Discovery OA PDF).CASGEVY USPI. CASGEVY (exagamglogene autotemcel) Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846. As of Revised 07/2026. Checked 2026-08-28. Type: Prescribing information.
  3. E2

    VERVE-101: enrollment paused after grade-3 ALT plus thrombocytopenia (8-K 2024-04-02). In-vivo base editing is not an established routine product.

    Verve 8-K. Form 8-K — Heart-1 pause. https://www.sec.gov/Archives/edgar/data/1840574/000119312524084067/d758833d8k.htm. As of 2024-04-02. Checked 2026-08-28. Type: SEC 8-K.
  4. E1

    Screening gaps: 200 bp until October 2026; oligo pools recommended, not required; SoC list not agreed. IGSC: no country requires providers.

    IGSC v3.1. Harmonized Screening Protocol Version 3.1. https://genesynthesisconsortium.org/wp-content/uploads/IGSC-Harmonized-Screening-Protocol-V3.1.pdf. As of 2026-06-01. Checked 2026-08-28. Type: Industry protocol.OSTP Framework. 2024 OSTP Framework for Nucleic Acid Synthesis Screening. https://aspr.hhs.gov/S3/Pages/OSTP-Framework-for-Nucleic-Acid-Synthesis-Screening.aspx. As of page as of 2026-08-28. Checked 2026-08-28. Type: US framework (HTML).
  5. E1

    Minimal cell ≠ understanding: 149 genes of unknown function; first design not viable.

    JCVI syn3.0. First Minimal Synthetic Bacterial Cell designed and constructed by scientists at the Venter Institute. https://www.jcvi.org/media-center/first-minimal-synthetic-bacterial-cell-designed-and-constructed-scientists-venter. As of 2016 (page). Checked 2026-08-28. Type: Institute page.Hutchison abstract. Design and synthesis of a minimal bacterial genome (abstract). https://www.jcvi.org/publications/design-and-synthesis-minimal-bacterial-genome. As of 2016. Checked 2026-08-28. Type: Abstract.
  6. E0

    iGEM: JS-only, no warrant in this entry.

6. Actors and incentives

Clinic, screening, lab

  1. E1

    FDA, Vertex/CRISPR Therapeutics (CASGEVY), bluebird (LYFGENIA), Frangoul NEJM early report — the label is the hardest approval source; Frangoul is an early report, not the label.

    FDA 2023-12-08. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. https://content.govdelivery.com/accounts/USFDA/bulletins/37efce0. As of 2023-12-08. Checked 2026-08-28. Type: Agency notice.CASGEVY USPI. CASGEVY (exagamglogene autotemcel) Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846. As of Revised 07/2026. Checked 2026-08-28. Type: Prescribing information.LYFGENIA PI. LYFGENIA (lovotibeglogene autotemcel) Prescribing Information. https://www.genetixbiotx.com/-/media/bluebirdbio/Corporate%20COM/Files/Lyfgenia/LYFGENIA_Prescribing_Information.pdf. As of Revised 12/2023. Checked 2026-08-28. Type: Prescribing information.Frangoul et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. https://doi.org/10.1056/NEJMoa2031054. As of published online 2020-12-05; NEJM 384:252–260 (2021-01-21); NCT03655678 / NCT03745287. Checked 2026-09-11. Type: Paper (NEJM; early clinical report).
  2. E1

    IGSC (industry), OSTP/ASPR (US funding condition), EO 14292 (revision announced, framework not updated as of 2026-08-28).

    IGSC v3.1. Harmonized Screening Protocol Version 3.1. https://genesynthesisconsortium.org/wp-content/uploads/IGSC-Harmonized-Screening-Protocol-V3.1.pdf. As of 2026-06-01. Checked 2026-08-28. Type: Industry protocol.OSTP Framework. 2024 OSTP Framework for Nucleic Acid Synthesis Screening. https://aspr.hhs.gov/S3/Pages/OSTP-Framework-for-Nucleic-Acid-Synthesis-Screening.aspx. As of page as of 2026-08-28. Checked 2026-08-28. Type: US framework (HTML).EO 14292. Executive Order 14292, Improving the Safety and Security of Biological Research. https://www.whitehouse.gov/presidential-actions/2025/05/improving-the-safety-and-security-of-biological-research/. As of 2025-05-05. Checked 2026-08-28. Type: Executive Order.
  3. E1

    JCVI (syn1.0/syn3.0) and Sc2.0/Goold (synXVI) — genomes as design objects.

    JCVI syn3.0. First Minimal Synthetic Bacterial Cell designed and constructed by scientists at the Venter Institute. https://www.jcvi.org/media-center/first-minimal-synthetic-bacterial-cell-designed-and-constructed-scientists-venter. As of 2016 (page). Checked 2026-08-28. Type: Institute page.Goold synXVI. Construction and iterative redesign of synXVI a 903 021 bp synthetic Saccharomyces cerevisiae chromosome. https://www.nature.com/articles/s41467-024-55318-3. As of 2025. Checked 2026-08-28. Type: Paper (Nature Communications).

7. State of the dispute

Governance vs. universal screening

  1. E1

    IGSC states explicitly: no country requires it. OSTP framework is a funding condition and in revision after EO 14292. HHS press 2026 is not the full policy.

    IGSC v3.1. Harmonized Screening Protocol Version 3.1. https://genesynthesisconsortium.org/wp-content/uploads/IGSC-Harmonized-Screening-Protocol-V3.1.pdf. As of 2026-06-01. Checked 2026-08-28. Type: Industry protocol.EO 14292. Executive Order 14292, Improving the Safety and Security of Biological Research. https://www.whitehouse.gov/presidential-actions/2025/05/improving-the-safety-and-security-of-biological-research/. As of 2025-05-05. Checked 2026-08-28. Type: Executive Order.HHS 2026-07-28. Trump Administration Releases New Government-Wide Policy to End Dangerous High-Risk Research. https://www.hhs.gov/press-room/stopping-high-risk-life-sciences-research.html. As of 2026-07-28. Checked 2026-08-28. Type: Press release.

8. Open questions

  1. Science Gibson 2010 / Hutchison 2016 full text.
  2. OSTP/HHS PDFs (fetch 500).
  3. WHO dual-use guidance 174-page PDF.
  4. Paddon 2013 artemisinin original.
  5. Fredens recoded E. coli.
  6. Ginkgo/Amyris SEC.
  7. iGEM statistics (not JS shell).

9. Changes

  • v1.2-draft2026-09-11: Frangoul et al. NEJM 2021 CTX001 (source 17, DOI 10.1056/NEJMoa2031054) opened — n=2 early report, editing/HbF/transfusion independence; governance only; n=2 ≠ label; no protocols/sequences/gRNAs.
  • v1.1-draft2026-09-04: Gillmore et al. NEJM 2021 NTLA-2001 (source 16, DOI 10.1056/NEJMoa2107454, UCL OA) opened — Phase-1 interim n=6, day-28 TTR −52%/−87%, no SAEs in report. Governance only; not an approval; no protocols/sequences.
  • v1.0-draftFirst version from the 2026-08-28 verification log. Dual-use as governance fact only.

10. Sources

No. Source As of Checked Grade
1 U.S. Food and Drug Administration. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. https://content.govdelivery.com/accounts/USFDA/bulletins/37efce0. Type: Agency notice. E1
2 Vertex Pharmaceuticals / CRISPR Therapeutics. CASGEVY (exagamglogene autotemcel) Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846. Type: Prescribing information. E1
4 bluebird bio. LYFGENIA (lovotibeglogene autotemcel) Prescribing Information. https://www.genetixbiotx.com/-/media/bluebirdbio/Corporate%20COM/Files/Lyfgenia/LYFGENIA_Prescribing_Information.pdf. Type: Prescribing information. E1
5 International Gene Synthesis Consortium. Harmonized Screening Protocol Version 3.1. https://genesynthesisconsortium.org/wp-content/uploads/IGSC-Harmonized-Screening-Protocol-V3.1.pdf. Type: Industry protocol. E1
6 ASPR / OSTP. 2024 OSTP Framework for Nucleic Acid Synthesis Screening. https://aspr.hhs.gov/S3/Pages/OSTP-Framework-for-Nucleic-Acid-Synthesis-Screening.aspx. Type: US framework (HTML). E2
7 ASPR. Synthetic Nucleic Acid Screening. https://aspr.hhs.gov/S3/Pages/Synthetic-Nucleic-Acid-Screening.aspx. Type: Agency page. E2
8 The White House. Executive Order 14292, Improving the Safety and Security of Biological Research. https://www.whitehouse.gov/presidential-actions/2025/05/improving-the-safety-and-security-of-biological-research/. Type: Executive Order. E1
9 U.S. Department of Health and Human Services. Trump Administration Releases New Government-Wide Policy to End Dangerous High-Risk Research. https://www.hhs.gov/press-room/stopping-high-risk-life-sciences-research.html. Type: Press release. E2
10 Verve Therapeutics. Form 8-K — Heart-1 pause. https://www.sec.gov/Archives/edgar/data/1840574/000119312524084067/d758833d8k.htm. Type: SEC 8-K. E2
11 J. Craig Venter Institute. First Minimal Synthetic Bacterial Cell designed and constructed by scientists at the Venter Institute. https://www.jcvi.org/media-center/first-minimal-synthetic-bacterial-cell-designed-and-constructed-scientists-venter. Type: Institute page. E1
12 J. Craig Venter Institute. First Self-Replicating Synthetic Bacterial Cell. https://www.jcvi.org/research/first-self-replicating-synthetic-bacterial-cell. Type: Institute page. E1
13 Hutchison, C. A. III; et al.. Design and synthesis of a minimal bacterial genome (abstract). https://www.jcvi.org/publications/design-and-synthesis-minimal-bacterial-genome. Type: Abstract. E1
14 Gibson, D. G.; et al.. Creation of a bacterial cell controlled by a chemically synthesized genome (abstract). https://www.jcvi.org/publications/creation-bacterial-cell-controlled-chemically-synthesized-genome. Type: Abstract. E1
15 Goold, H. D.; et al.. Construction and iterative redesign of synXVI a 903 021 bp synthetic Saccharomyces cerevisiae chromosome. https://www.nature.com/articles/s41467-024-55318-3. Type: Paper (Nature Communications). E1
16 Gillmore, J. D.; et al.. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. https://doi.org/10.1056/NEJMoa2107454. Type: Paper (NEJM; UCL Discovery OA PDF). E1
17 Frangoul, H.; Altshuler, D.; Cappellini, M. D.; Chen, Y.-S.; Domm, J.; Eustace, B. K.; Foell, J.; de la Fuente, J.; Grupp, S.; Handgretinger, R.; Ho, T. W.; Kattamis, A.; Kernytsky, A.; Lekstrom-Himes, J.; Li, A. M.; Locatelli, F.; Mapara, M. Y.; de Montalembert, M.; Rondelli, D.; Sharma, A.; Sheth, S.; Soni, S.; Steinberg, M. H.; Wall, D.; Yen, A.; Corbacioglu, S.. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. https://doi.org/10.1056/NEJMoa2031054. Type: Paper (NEJM; early clinical report). E1

11. Uncertainty log

Overall uncertainty of this entry, bound to the verification log of 2026-08-28 plus Gillmore (2026-09-04) and Frangoul (2026-09-11). 16 opened sources (one duplicate label number). Dual-use as governance only. No protocols, sequences, oligos, gRNAs, assembly recipes.

  • Established (layer 1): CASGEVY label 07/2026; Frangoul CTX001 early report n=2 (17); Gillmore NTLA-2001 Phase-1 interim (16); LYFGENIA boxed warning; IGSC no mandate; syn1.0/syn3.0; synXVI design bugs.
  • Claimed (layer 2): HHS press; JCVI prose; in-vivo framing beyond Gillmore interim.
  • Constrained (layer 3): CRISPR ≠ outpatient; Frangoul n=2 ≠ Phase-3/label; in-vivo ≠ approved (Gillmore interim vs CASGEVY label); VERVE-101 pause; screening gaps 200 bp; minimal cell ≠ understanding; iGEM E0.

Not opened (not a warrant)

  • Science Gibson / Hutchison full text.
  • OSTP/HHS PDFs HTTP 500.
  • WHO dual-use 174 pages.
  • Paddon 2013.
  • Fredens recoded E. coli.
  • Ginkgo/Amyris SEC.
  • iGEM (JS-only).