Environmental Inheritance, the RNA Layer, and the Path to RNA Vaccines and Gene Therapy

This is a self-contained volume of the VP (jamming-physics) framework. From asingle physical substrateit derives themechanisms of transgenerational environmentalinheritance, the small-RNAwritable channel, immunememory and maturation,RNA vaccines, and gene therapy. The organizingthesis is that thegenome is read on twochannels: the SET — thepromoter ruler γ thatscales a bistable switchand is fixed in thegenome, so the environmentcannot rewrite it — andthe A4 COORDINATE —where an element sits in a compartment-shell/anchor-looparchitecture and whether it is onthe same helical face as its anchor (contact-competent). The environmentwrites a reversible driveh, and it doesso through the A4 channel(and methylation),never through γ; asmall RNA acts by sequencecomplementarity, naming an A4coordinate and depositing adrive there.

Everyresult stands on onevendored primitive, theR19 jamming switchds/dt = γ·s − s³ +h: a double wellwhose flip thresholdis the spinodal2(γ/3)^1.5 and whoseinter-basin barrier — state stability, hence memory —is γ²/4. No γ isfitted. Each γ ismeasured as the mean nearest-neighbour stacking freeenergy (SantaLucia1998) over the promoterwindow TSS−2000..+500on GRCh38,and the measurementpipeline is acceptedonly because itreproduces the SOX9anchor bit-for-bit at γ =1.4598 (GC =0.545). The germline, immune,RNA-machinery, imprinted,autism, cancer and neurodegeneration γ atlases arefrozen regression checkpoints.

The volume runseighteendeterministic discriminantbatteries (R, RS, A4, TC,TG, GE, CH, I, IM,V, GT, AM, FM, DM,FV, PO, VK, LV), allgreen. Small RNA is a reversible, signed write ofthe drive, resolvedby measured biogenesis machinery intomiRNA/piRNA/tsRNA/m6A. The A4coordinate channel is orthogonal to γ —γ tracks promoter GC at R² ≈ 69%, butthe helical contact phase is ≈ 98%independent — so γ alone is degenerateand A4 is the writable, RNA-targetedchannel. Environment-to-germlinetransmission is gated by areprogramming firewall that squares amark's survival probability (p²), withheritability ranking by barrier depth (ascending-γ, Spearman ρ → 1.0); on the measured imprinted-escapee atlas survival ranks ascending-γ (ρ = 1.0). Immune memory is a held basin whose lifetime ranks ascending-γ; affinity maturation emerges from an iterated germinal-centre loop with an interior optimum in selection stringency (survivor-fraction 0.4), and innate-vs-adaptive durability is a two-timescale split (MFPT ratio ≈ 2.37). An RNA vaccine is a supra-spinodal flip into a protected basin held by the barrier, with an interior boost-schedule optimum. Gene therapy resolves into exactly two levers: Lever A edits the SET (moves the threshold, irreversible by a drive) and Lever B resets the drive reversibly via RNA, the choice set by a geometry threshold. Parent-of-origin is a duration asymmetry — a sustained maternal drive flips a switch that a transient paternal bolus does not — and is universal across the germline atlas (13/13).

The volume is explicit about the boundary between an internal map (A) and external evidence (B). On the ordering axis the held-out score is reported as-it-falls: scored against held-out Replogle 2022 CRISPRi knockdown depth (γ frozen from DNA before any expression was seen), it is a recorded NULL (ρ = −0.08, p = 0.63) that promotes nothing, and a GC-identifiability stress test shows every γ-ordered prediction is non-identified as a class. The sole crossing to evidence that is both identified (orthogonal to GC) and firewall-clean is the corrective sign-law: the mechanism-forced sign (loss-of-function → "+" restore, gain-of-function → "−" knockdown) is orthogonal to γ (point-biserial ≈ −0.015). This sign-law is validated bidirectionally on independent held-out data: its "−" arm on held-out DepMap CRISPR-knockout (gain-of-function oncogenes are dependencies, loss-of-function suppressors are not — point-biserial = +0.494, exact p = 0.0227) and its "+" RESTORE arm on held-out Horlbeck 2016 CRISPRa (loss-of-function suppressors are growth-suppressive on activation, gain-of-function oncogenes are not — point-biserial = +0.4852, exact p = 0.0274). These are the volume's first and second held-out positives, making the corrective sign-law bidirectionally verified, direction-only.

All claims are direction-only behind a magnitude firewall: the volume reads WHICH switch is tilted, the SIGN of the drive, and the ORDERING / DECAY / BOUNDARY of inheritance and memory — never an absolute phenotype, dose, titre, penetrance or generation-count, which remain runtime-open and are named in the irreproducibility ledger. Every clinical application (vaccination, gene therapy, fertility care) is explicitly handed to clinicians and regulators.

The complete runnable kit is attached to this record as vp_inheritance_kit_v0_19_0.zip (internal root vp_inheritance_kit/). It carries the vendored substrate, the measured γ atlases and their offline promoter caches, the research engines, and a deterministic gate. To reproduce, run python repro/run_all.py: it recomputes the RNA-machinery γ from the cached promoters (the SOX9 no-tuning gate), runs the eighteen batteries, and applies a 2×SHA-256 determinism gate, writing reports/research_complete.json with all_green = true. The PDF in this record is the canonical HTML rendered to print (VP-SPEC v1.8).

Author: Young Jae Lee (ORCID 0009-0002-7535-8245). License: CC BY 4.0. Published at jamming-physics.org/inheritance/. Source and reproduction: github.com/rego093-sketch/jamming-physics. Concept DOI 10.5281/zenodo.20783547 (resolves to the latest version).