Decision spine
Frames the controlling thesis, evidence status, buyer implications, and research-use limits.
Gene Therapy
Zemi Dossier
Research-use only
Epigenome Editing & Tunable Permanence
A decision package on whether epigenome-editing programs can translate liver durability into durable, reversible, and clinically meaningful control across loci, tissues, and reservoirs.
Decision this dossier helps answer
Which epigenome-editing programs have a defensible durability strategy, and what decay force would erase the imposed mark before benefit is proven?
Problem this dossier solves
Durability is a vector, not a half-life.
The updated dossier argues that epigenome-editing durability is governed by three separable decay forces: mitotic dilution, active erasure, and reactivation pressure. The Borrowed-Durability Ledger and DLF classifier help buyers distinguish liver-anchored durability from the unresolved extrahepatic and human frontier.
What is moving: current field evidence and platform activity
What is unresolved: decision-grade proof, endpoint logic, and failure modes
What Zemi solves: evidence-gated next-study strategy
Full decision package
96-page research report plus 38-sheet Evidence & Decision Workbook
Buy now
$3,500$5,500Launch price
Controlling thesis
Durability is a vector, not a half-life.
The updated dossier argues that epigenome-editing durability is governed by three separable decay forces: mitotic dilution, active erasure, and reactivation pressure. The Borrowed-Durability Ledger and DLF classifier help buyers distinguish liver-anchored durability from the unresolved extrahepatic and human frontier.
A Zemi Dossier turns uncertain emerging research into a decision package: what is known, what is inferred, what is hypothetical, what would falsify the thesis, and what should be built, funded, avoided, monitored, or validated next.
Research report preview
First 30 pages of the actual Epigenome Editing & Tunable Permanence research report.
The public page shows the real document style, density, evidence posture, and decision framing before a buyer requests access to the full Zemi Dossier package.
Research report
The research report is the argument. It is not the whole product.
The PDF research report is the structured argument: field status, evidence maturity, buyer implications, falsifiable hypotheses, power-calculated next studies, strategic recommendations, limitations, and traceability posture.
Inspectable infrastructure
Pairs the report with claim ledgers, evidence tables, power rows, audit surfaces, and decision tools.
Executable next studies
Links hypotheses to endpoint logic, assumptions, sample-size logic, budget, and timeline planning.
Research report table of contents
Public TOC generated from the source report.
The full research report is delivered as a licensed PDF. This table shows the decision structure without publishing the full product.
| Section | What it covers | Buyer value |
|---|---|---|
| Decision Brief Read This First | Turns the report into immediate buyer triage: what matters now, what is still uncertain, and what to do next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Contents | Shows the report structure and where to inspect the argument, evidence, workbook logic, and limits. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Executive Summary | Condenses the dossier thesis, evidence posture, buyer implications, and next-study priorities. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Scope and Evidence Integrity | Defines the evidence window, source boundaries, research-use limits, and labeling discipline. | Lets the buyer audit support strength before relying on the package. |
| Methodology and Search Strategy | Shows how strong the source base is and where conclusions depend on indirect or thinner support. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Decision Snapshot Overview | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buyer Decision Dashboard | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buy Build Wait Avoid | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buyer Decision Matrix | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Source Quality Dashboard | Shows how strong the source base is and where conclusions depend on indirect or thinner support. | Lets the buyer audit support strength before relying on the package. |
| Central Thesis Model | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The Borrowed Durability Ledger | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Current Signal Update 2025 2026 | Frames the field's June 2026 state, active programs, research fronts, and timing signals. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| June 2026 currentness addendum | Frames the field's June 2026 state, active programs, research fronts, and timing signals. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Cross Axis Convergence Map | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Cross Study Cross Domain Synthesis | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Evidence Maturity and Modality Matrix | Links claims to source support so users can separate what is known, inferred, and hypothetical. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Comparative Modality Mechanism Matrix | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Proprietary Classifier Dlf | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Key Findings | Summarizes the most decision-relevant findings and their implications for the dossier thesis. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The modality | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Borrowed durability | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Read-write self-reinforcement | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Hit-and-run heritability | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Conflict principle (reactivation) | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Processivity-coupling | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Transient delivery | Identifies translational, regulatory, safety, or delivery constraints that shape whether the thesis can be tested. | Shows where the thesis could fail or require more validation before action. |
| Division-Currency | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Hepatic flagship (NHP-durable) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Activation / imprinting | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Same-Switch reversibility | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Off-target methylation-spread | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Extrahepatic cliff | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Episome-Exception (cccDNA) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Permanence spectrum | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Immune-cell engineering | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
Evidence & Decision Workbook
The workbook is the decision engine.
A locked public preview of selected workbook-derived sheets: sheet structure, decision modules, power rows, traceability, and audit posture. Licensed buyers receive the full workbook files.
Read-only workbook preview with clipped values and no formulas. Licensed buyers receive the full Evidence & Decision Workbook with editable assumptions and working files.
Workbook inventory
Delivered workbook sheets.
Full inventories belong on dossier pages, not the homepage. Sheet names below are extracted from the actual workbook file.
| # | Workbook sheet | What it does |
|---|---|---|
| 1 | 1. Workbook Guide | Navigation layer for using the workbook, understanding sheet roles, and following the decision package. Public preview exposes Dossier, Epigenome Editing and Tunable. fields and clipped entries such as Controlling model, The Borrowed-Durability Ledger:.,. |
| 2 | 2. Claim Ledger | Claim-by-claim ledger showing verdicts, source support, inference status, and decision relevance. Public preview exposes claim_id, source IDs, source type, study design fields and clipped entries such as kf-transient, PMID:40335752, PubMed-indexed. |
| 3 | 3. Evidence Table | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes NCT:NCT06907875, A Phase 1/2 Open-label., ClinicalTrials.gov, 2025-05-08 fields and clipped entries such as NCT:NCT07428473, A Phase 1 Open-Label. |
| 4 | 4. Source-Support Verdicts | Independent check on whether key claims are actually supported by cited sources. Public preview exposes PMID:40715076, Finding 2 — UHRF1 mediates HBG., SUPPORTS_EXACTLY, β-hemoglobinopathies caused by. fields and clipped entries such as. |
| 5 | 5. Source-Quality Summary | Summary of source strength, gaps, and areas where conclusions depend on weaker evidence. Public preview exposes Audited claims, 147 = 65 kept + 82 excluded (75. fields and clipped entries such as Customer-facing claims, 67 customer-facing + 2 quarantined =.,. |
| 6 | 6. Editor & Modality Scorecard | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Editor / effector, Mark written, Durability, Reversible fields and clipped entries such as CRISPRoff (dCas9-ZIM3-KRAB-DNMT3A/3L), DNA methylation +. |
| 7 | 7. Locus-Heritability & Durabil | Segments the field by relevant biology so buyer decisions are not overgeneralized. Public preview exposes Locus, Tissue, Effector, Modality fields and clipped entries such as HBG, HUDEP2 / CD34+, UHRF1 / demethylation. |
| 8 | 8. Reversibility & Redosing | Workbook surface supporting a specific evidence, decision, study-planning, or release-control workflow. Public preview exposes Locus / property, Reversibility evidence, Maturity, Source fields and clipped entries such as HBG (erythroid), silencing reversed. |
| 9 | 9. Off-Target - Methyl-Spread | Captures failure modes and constraints that could invalidate or narrow a program. Public preview exposes Axis, Finding, Assay, Source fields and clipped entries such as Multimerised DNMT3A, widespread early off-target., WGBS. |
| 10 | 10. Delivery-by-Tissue (cliff) | Segments the field by relevant biology so buyer decisions are not overgeneralized. Public preview exposes Tissue, Status, Vehicle, Assets / evidence fields and clipped entries such as Liver, SOLVED, LNP; hepatotropic AAV. |
| 11 | 11. Clinical-Asset & Company | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Asset, Company, Target/locus, Indication fields and clipped entries such as EPI-321, Epicrispr Biotechnologies, DUX4. |
| 12 | 12. Trial - Catalyst Tracker | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Asset, NCT, Status, Primary completion fields and clipped entries such as EPI-321, NCT06907875, RECRUITING. |
| 13 | 13. Comparative-Modality Matrix | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Modality, Cuts DNA?, Permanence, Reversible? fields and clipped entries such as Epigenome editing, Tunable (locus-set), YES (hysteresis-limited). |
| 14 | 14. Regulatory & Endpoint | Tracks regulatory, endpoint, reimbursement, or qualification requirements that shape testing strategy. Public preview exposes Issue, Standard / approach, Why (verified), Source fields and clipped entries such as Durability-proof endpoint,. |
| 15 | 15. Figure Source Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes Fig #, Figure ID, title, family fields and clipped entries such as fig04_decision_snapshot, Readiness verdicts grading the.,. |
| 16 | 16. Figure Attempt Ledger | Figure and numeric reproduction log for validating calculations, chart inputs, or displayed values. Public preview exposes Figure ID, Family, Backend, Data type fields and clipped entries such as fig01_grade_recalibration, evidence_grade_distribution,. |
| 17 | 17. Hypotheses Ledger | Maps hypotheses to evidence state, falsification logic, endpoints, and next-study design. Public preview exposes #, Tier / class, Axis / title, Hypothesis fields and clipped entries such as F1, Flagship, The Durability-Limiting-Factor (DLF).. |
| 18 | 18. Most Valuable Next Studies | Prioritizes next studies that could change the decision, including endpoints and evidence gates. Public preview exposes study_id, hypothesis_tested, study_title, research_question fields and clipped entries such as MVNS1, F1, Turnover-challenge DLF. |
| 19 | 19. Verification & Search Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes Source / API, Query / scope, Volume, Result fields and clipped entries such as NCBI E-utilities / references registry, PMID metadata +. |
| 20 | 20. Excluded Claims (82) | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes Excluded claim, Citations, Bucket, Disposition fields and clipped entries such as Excluded 8 — CAR-T cell therapy has.,. |
| 21 | 21. Quarantine + Salvage | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes Item, Recovered as, Source, Note fields and clipped entries such as STX-1150 (liver-targeted epigenetic., Clinical asset -. |
| 22 | 22. Power Calculations | Power-calculation layer for assumptions, endpoint logic, computed sample sizes, and sensitivity checks. Public preview exposes hypothesis_id, study_id, endpoint, test_type fields and clipped entries such as F1, DLF-VAL-01, Held-out dominant-decay-force AUC. |
| 23 | 23. Score Basis | Explains how scores or ratings were assigned so the decision instrument can be inspected. Public preview exposes Score (figure), Scale, What each level means, Basis (how assigned) fields and clipped entries such as Buyer near-term actionability (fig 11), 1-3. |
| 24 | 24. Competitive Landscape | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Company, Asset, Modality / effector, Target / tissue fields and clipped entries such as Scribe Therapeutics, STX-1150 (+ELXR platform), Epigenetic. |
| 25 | 25. DLF Input Template | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes evidence_completeness, Complete, Complete | Partial | Sparse, Partial/sparse triggers MIXED /. fields and clipped entries such as rescue_risk, Low,. |
| 26 | 26. DLF Feature Scores | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes class_label, score_formula, turnover_component, activator_component fields and clipped entries such as DILUTION_LIMITED, Fast-turnover tissue or. |
| 27 | 27. DLF Class Output | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes source_directness, Adjacent / hypothesis-generating. fields from this sheet. |
| 28 | 28. DLF Decision Rules | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes DILUTION_LIMITED, top score and margin >=1.25;., Lead post-mitotic/slow-turnover., serial passage / regeneration. fields and clipped entries such. |
| 29 | 29. DLF Archetype Cards | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes card, turnover, activator, TET fields and clipped entries such as Hepatic PCSK9 easy corner, Slow, Low. |
| 30 | 30. DLF Minimum Assay Panel | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes assay, input supported, minimum QC, source fields and clipped entries such as WGBS / targeted bisulfite, Baseline methylation + off-target DMRs,. |
| 31 | 31. DLF Validation Log | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes functional_endpoint, durability delta and. fields and clipped entries such as comparator_baseline, naive one-size epigenetic editor /., status. |
| 32 | 32. DLF Traceability Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes classifier_surface, report/workbook linkage, source_or_claim_ids, purpose fields and clipped entries such as Input Template, Claim Ledger. |
| 33 | 33. Version Registry | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes date, version/event, change_summary, status fields and clipped entries such as 2026-06-16, REV-4 builder remediation, Integrated. |
| 34 | 34. Audit Issues Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes finding_id, status, builder_fix fields and clipped entries such as MF1 Currentness, closed, Integrated Tune-401 EASL 2026 May 30.. |
| 35 | 35. Traceability Certificate | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes claim_id, report_section/page, report_page, claim_text fields and clipped entries such as kf-transient, establishment/delivery,. |
| 36 | 36. Newest Material Signals | Tracks biomarkers or readouts that determine whether the thesis is moving toward testable evidence. Public preview exposes signal, Present / Missing, Sponsor-reported / Peer-reviewed., materiality / boundary fields and clipped entries such as VERVE-102,. |
| 37 | 37. Source-Support Registry | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes source_id, identifier_type, identifier_value, title fields and clipped entries such as PMID:17994007, PMID, The SRA protein Np95 mediates.. |
| 38 | 38. Figure Reproduction Log | Figure and numeric reproduction log for validating calculations, chart inputs, or displayed values. Public preview exposes figure_id, plotted_row_or_key, plotted_value_or_coordinate, workbook_or_source_rows fields and clipped entries such as. |
Power-calculated next studies
Power calculations are the execution bridge.
Power calculations are planning-grade research calculations for endpoint logic, assumptions, sample size, budget, and timeline. They do not prove hypotheses or constitute clinical protocol.
| Hypothesis | Primary endpoint | Test | Effect | α | Power | Computed n | Design n |
|---|---|---|---|---|---|---|---|
| F1 | Held-out dominant-decay-force AUC | AUC (Hanley-McNeil, external) | 0.8 | 0.05 | 0.80 | 72 | 90 |
| F2 | Durability vs off-target correlation | Correlation (Fisher-z) | 0.6 | 0.05 | 0.80 | 26 | 29 |
| F2 | Transient vs constitutive off-target burden | Two-sample means (Cohen d) | 2.31 | 0.05 | 0.80 | 3 | 12 |
| F3 | LDL-C restoration after deliberate reversal | Two-sample means (Cohen d) | 1.67 | 0.05 | 0.80 | 6 | 18 |
| F4 | Functional cure proportion at 6 months | Two-proportion, pooled | 0.5 | 0.05 | 0.80 | 27 | 70 |
Release audit discipline
Audit posture is part of the product.
Public pages do not publish exact audit scores. They should state the release discipline, revision posture, and limitations without implying peer review or validated clinical guidance.
Research-use decision package
Not medical advice, clinical guidance, investment advice, or a clinical protocol.
Known / inferred / hypothetical
The package separates cited evidence from inference and frontier hypothesis generation.
Audit-gated and revision-controlled
Adversarial audit checks source support, formulas, figures, limitations, and release readiness.
Buy this dossier
Full decision package — 96-page report + 38-sheet workbook
Buy now
- Decision research report (96 pages, PDF)
- Evidence & Decision Workbook (38 sheets, .xlsx) — claims, source-support verdicts, power calculations, traceability, and audit log
- Live, editable power-calculated next studies
$3,500$5,500Launch price