A public reference catalog of aging-dysregulated human miRNAs with integrated dossiers. The catalog is published as field infrastructure: an academic group, a biotech R&D team, or a generics manufacturer can pick a candidate and start work without rebuilding the upstream curation. Every literature claim is sourced to primary publication via PubMed / DOI; every freedom-to-operate verdict is reproducible from the bundled per-pair clearance JSON against the named 5,596-patent corpus on the snapshot date.

What this is

An open reference catalog. The bundle ships under CC-BY-4.0 with no clinical or therapeutic claim attached: predicted target footprints, tissue exposure scores, and senescence-associated overlay annotations are computational predictions calibrated against literature. Bench validation and clinical trials remain the standard for therapeutic assertions. The catalog asserts only that the curation, classification, and clearance verdicts are reproducible from the bundled artifacts.

The architectural commitment is sharp: for each of 84 atomic candidate miRNAs, the catalog reports the López-Otín hallmark coverage from the audited literature evidence, the centenarian-signature direction and confidence per cohort, the freedom-to-operate verdict at six antisense modulator chemistries (LNA-2'-MOE-PS gapmer 16 nt, 2'-MOE-PS gapmer 22 nt, mimic 22 nt, GalNAc-2'-MOE-PS gapmer 16 nt, PMO 22 nt, tough-decoy 60 nt), the predicted target footprint × GTEx v8 tissue-expression product across ten aging-relevant tissues, the mouse and rat ortholog list with seed-family coverage, the SenMayo senescence-associated secretory phenotype overlay statistics, the top 15 HIGH-tier predicted targets, the full audited literature evidence rows per candidate, and the citation list.

Hero candidate: miR-130a-3p

miR-130a-3p is the single candidate in the catalog that hits all three independent evidence axes simultaneously: senescence-associated secretory phenotype enrichment, centenarian-preserved direction, and IP-clean canonical antisense chemistry.

AxisResult
SenMayo SASP overlaytop-500 predicted binders contain 12 SenMayo signature genes (log2 FE 1.917, hypergeometric p = 8.3 × 10⁻⁵). Hits include EREG, IGF1, IL15, TNFRSF1B, MMP10, MMP13, TNF, IGFBP5.
Centenarian classificationpreserved-LLI in the German-Kiel PBMC cohort (ElSharawy 2012, Aging Cell; confidence MEDIUM).
IP-clearance at canonical chemistryCLEAR at LNA-2'-MOE-PS gapmer 16 nt: HIGH = 0, MEDIUM = 0, LOW = 2,482 across the 5,596-patent corpus.
Cross-species coverageFULL_3SPECIES: 8 mouse orthologs, 4 rat orthologs (mmu-miR-130a/b/c, mmu-miR-301a/b, rno-miR-130a/b, rno-miR-301a/b, plus seed-family).
Top tissue (raw repressive footprint)vasculature.
Top tissue (enrichment)skin.

The combination is unique in the catalog. No other candidate reaches DIRECT_SASP at top-500, sits in the centenarian-preserved-LLI signature, AND clears canonical LNA-2'-MOE-PS gapmer 16 nt without HIGH or MEDIUM patent flags. The full dossier — including the SenMayo target table, the cross-species ortholog list, the cleanest-chemistry recommendation, and the audited literature evidence rows — is in dossiers/miR-130a-3p.md in the bundle.

What's in the catalog

FieldValue
Atomic candidates with full dossiers84
Distinct biological miRNA cores (literature evidence)302
Audited literature evidence rows559
A-grade primary-source verified464 (83.0%)
López-Otín hallmarks covered12 / 12
Centenarian-preserved-LLI signature21 across 6 cohorts
Intervention-responsive miRNAs24 post-CrossRef-audit
Freedom-to-operate pairs504 (84 × 6 chemistries)
Patents scanned5,596 across 252 assignees

Headline subsets

Twenty-five canonical-clean publishable candidates

Twenty-five candidates pass the canonical LNA-2'-MOE-PS gapmer 16 nt chemistry without any HIGH or MEDIUM patent encumbrance flag against the 5,596-patent corpus. These can be published and synthesised at canonical antisense specificity without licensing concern against the surveyed patents.

The remaining 47 of the 72 atomic candidates scored at canonical chemistry require a design-around chemistry (mimic 22 nt, PMO 22 nt, GalNAc-2'-MOE-PS gapmer 16 nt, or tough-decoy 60 nt) to clear. The dossier ## IP-clearance section names the cleanest available chemistry for each encumbered candidate.

Six IP-clean DIRECT_SASP candidates (SASP-axis senolytic leads)

The SenMayo SASP overlay (Saul et al. 2022 Nat Commun 13:4827, 125-gene human signature; 124 in atlas after CCL3L1 absence) tests whether each candidate's top-N strongest predicted binders are over-enriched for senescence-associated secretory phenotype genes via a hypergeometric over-representation test. Eight candidates pass DIRECT_SASP at top-500 with hypergeometric p < 0.05; six of these are also IP-clean at canonical LNA-2'-MOE-PS gapmer 16 nt.

CandidateTop-500 SenMayo kLog2 FEpCentenarianIP canonical
miR-130a-3p121.9178.3 × 10⁻⁵preserved-LLI MEDIUMCLEAR
miR-130b-3p121.9178.3 × 10⁻⁵—CLEAR
miR-148a-3p91.5024.7 × 10⁻³—CLEAR
miR-148b-3p91.5024.7 × 10⁻³—CLEAR
miR-152-3p91.5024.7 × 10⁻³—CLEAR
miR-365a-3p71.1404.1 × 10⁻²—CLEAR
miR-19a-3p91.5024.7 × 10⁻³—ENCUMBERED
miR-19b-3p91.5024.7 × 10⁻³preserved-LLI MEDIUMENCUMBERED

The six IP-clean DIRECT_SASP candidates are publishable at canonical antisense specificity and are the natural starting point for a senolytic discovery program targeting the SASP axis directly via miRNA modulation. The two ENCUMBERED candidates (miR-19a/b-3p) clear at design-around chemistries (mimic 22 nt, PMO 22 nt, tough-decoy 60 nt).

Tier structure

Tiers reflect literature-evidence depth, not therapeutic priority. A Tier 3 candidate may be the strongest pick for a specific research question if its target footprint, tissue exposure, or SASP overlay matches the use case.

TierDefinitionAtomic count
T1Multi-hallmark anchors (≥ 3 López-Otín hallmarks); deepest literature support10
T2Two-hallmark coverage; well-supported in primary literature29
T3Single-hallmark coverage including paralog clusters and SASP-axis discovery45
Total—84

Centenarian-signature classification

Each candidate carries a centenarian-signature direction (preserved-LLI vs mortality-associated), a cohort list with PubMed / DOI anchors, methods consistency rating, tissue, and a confidence label (HIGH / MEDIUM / LOW). The 21-row centenarian-preserved-LLI signature is sourced to six independent cohort studies:

Antisense modulator palette

ChemistryBackboneLengthCatalog clearance
LNA-2'-MOE-PS gapmerlocked-nucleic-acid wings, 2'-MOE wings, phosphorothioate backbone16 nt35% clean
2'-MOE-PS gapmer2'-O-methoxyethyl wings, phosphorothioate backbone (no LNA)22 ntnon-LNA fallback
mimic22 nt double-stranded RNA mimic22 nt≈ 75% clean
GalNAc-2'-MOE-PS gapmer16-nt gapmer with N-acetylgalactosamine conjugate16 ntliver-targeted via ASGPR
PMOphosphorodiamidate morpholino oligomer (no PS, no LNA)22 nt≈ 75% clean
tough-decoydual-target tough-decoy expression cassette60 nt100% clean (universal fallback)

Tough-decoy 60 nt is universal-clean across all 84 candidates (504 / 504 pairs at status CLEAR with 0 HIGH and 0 MEDIUM) and serves as a fallback chemistry for any candidate that fails canonical clearance.

Freedom-to-operate methodology

For each (candidate, chemistry) pair, every claim of every patent in the 5,596-patent corpus is scored against the candidate at one of three severity levels: HIGH (claim language reads directly on the candidate sequence + chemistry), MEDIUM (claim language reads on a structurally close variant or generic class containing the candidate), LOW (distant overlap). The clearance verdict per pair (status: CLEAR | ENCUMBERED) is derived from HIGH and MEDIUM counts: a pair is CLEAR if HIGH = 0 and MEDIUM ≤ 1.

Per-pair JSON in clearance/ in the deposit carries the full HIGH and MEDIUM patent ID list for any verdict so a downstream developer can re-verify against the named claims via the USPTO / EPO public databases.

The clearance check is freedom-to-operate due diligence, not a §102 prior-art filing. The catalog does not assert that any claim is invalid; it asserts only that the candidate sequence + chemistry, as published in this catalog at the dossier-described specificity, does not read on a HIGH-severity claim of any surveyed patent on the corpus snapshot date.

What each dossier contains

A dossier (dossiers/<candidate>.md) is generated deterministically from the bundled audited tables and the predicted target atlas. Each dossier carries family + tier + miRBase v22 ID; López-Otín hallmark coverage; centenarian-signature classification with cohort list, methods, tissue, therapeutic implication, caveat, and confidence; per-chemistry clearance verdict with HIGH/MEDIUM/LOW counts; recommended cleanest chemistry; predicted target footprint × GTEx v8 tissue exposure (top 3 by raw repressive footprint, top 3 by enrichment); cross-species translation with mouse and rat orthologs; top conserved targets ranked by TargetScan weighted context score; SenMayo SASP overlay statistics with top SenMayo hits ranked by binding affinity; top 15 HIGH-tier predicted targets; full catalog evidence rows; PubMed / DOI reference list.

How to use the catalog

  1. For the cleanest 3-axis senolytic candidate — pick miR-130a-3p (DIRECT_SASP + centenarian-preserved + IP-clean canonical). Open dossiers/miR-130a-3p.md.
  2. For a panel SASP-axis program — pick the 6 IP-clean DIRECT_SASP candidates above. All clear at canonical LNA-2'-MOE-PS gapmer 16 nt.
  3. For a cross-hallmark anchor — pick a Tier 1 multi-hallmark candidate from dossiers/INDEX.md (let-7a-5p, miR-29a-3p, miR-21-5p, miR-126-3p, miR-181a-5p). All Tier 1 candidates have ≥ 3 hallmark coverage; all clear at the dossier-named recommended chemistry; many carry HIGH centenarian confidence.
  4. For tissue-targeted programs — filter tsvs/tissue_exposure.tsv for the target tissue's top-enrichment candidates.
  5. For a generics-manufacturer entry point — pick any of the 25 canonical-clean publishable miRNAs and synthesise the recommended chemistry at the named specificity.

Download

The deposit consists of one PDF (the catalog overview, 10 pages) plus one zip bundle (84 dossiers + 9 audited TSVs + 504 per-pair clearance JSONs + README + LICENSE).

PDF:    aging-mirna-platform.pdf  (≈ 350 KB, 10 pages)
Bundle: aging-mirna-platform-bundle.zip  (≈ 48 MB, 603 files)
        - README.md
        - LICENSE (CC-BY-4.0)
        - dossiers/  (84 + INDEX.md)
        - tsvs/      (9 audited tables)
        - clearance/ (504 per-pair JSONs)
License: CC-BY-4.0
Zenodo:  https://doi.org/10.5281/zenodo.19952344

The predictor implementation that produces the binding-affinity numbers underlying the target footprints is held proprietary and is not distributed with this catalog. Inquire for commercial licensing or for custom-catalog commissions covering additional candidate axes (cell-type resolution, additional senescence panels, indication-stratified prioritisation, combination protocols).

Citation

If you use this catalog in published work, please cite:

Coracle Research (2026). Aging miRNA reference catalog: 84 candidates
with integrated hallmark, centenarian-signature, target-footprint,
tissue-exposure, SASP overlay, and 504-pair IP-clearance dossiers
across six antisense modulator chemistries.
Zenodo. https://doi.org/10.5281/zenodo.19952344

Foundational references: