{
  "metadata": {
    "generated_at": "2026-10-23T07:26:00Z",
    "tier": "Tier T0/T1 Exploratory In Silico Hypothesis (Unverified Parametric Constants)",
    "schema_version": "1.0.0",
    "source_code_hash": "69510bf81da723492952670a988ff2217ef47e62aca22cc29724647ff2ee195b",
    "doi_citations": [
      "10.1126/scitranslmed.3002230",
      "10.1084/jem.20020400",
      "10.1016/j.addr.2006.07.019",
      "10.1038/nature12777",
      "10.1038/nature14553",
      "10.1016/j.stem.2009.04.002",
      "10.1016/j.stem.2016.11.001",
      "10.3389/fonc.2013.00216",
      "10.1073/pnas.1813020116",
      "10.1016/j.bioactmat.2024.03.017",
      "10.1016/S2213-2600(15)00245-3"
    ],
    "terms_of_use": "Exploratory in silico hypothesis / unverified parametric constants only. Not primary empirical evidence and not medical advice."
  },
  "json_ld": {
    "@context": "https://schema.org",
    "@type": "Dataset",
    "name": "Cross-Domain Stem Cell Delivery Breakthrough Models for Cystic Fibrosis",
    "description": "Deterministic in silico biophysical and kinetic models establishing feasibility for apical-to-basolateral receptor transcytosis (FcRn, TfR1, pIgR), airway secretory-to-basal dedifferentiation plasticity, and cross-domain delivery innovation rankings.",
    "license": "https://creativecommons.org/licenses/by/4.0/",
    "citation": [
      "https://doi.org/10.1126/scitranslmed.3002230",
      "https://doi.org/10.1084/jem.20020400",
      "https://doi.org/10.1016/j.addr.2006.07.019",
      "https://doi.org/10.1038/nature12777",
      "https://doi.org/10.1038/nature14553",
      "https://doi.org/10.1016/j.stem.2009.04.002",
      "https://doi.org/10.1016/j.stem.2016.11.001",
      "https://doi.org/10.3389/fonc.2013.00216",
      "https://doi.org/10.1073/pnas.1813020116",
      "https://doi.org/10.1016/j.bioactmat.2024.03.017",
      "https://doi.org/10.1016/S2213-2600(15)00245-3"
    ]
  },
  "datasets": {
    "bfi_rankings": [
      {
        "id": "CDI-004",
        "title": "Airway Secretory-to-Basal Dedifferentiation via Transient Notch Reprogramming",
        "donor_field": "epithelial_plasticity",
        "primary_doi": "10.1038/nature12777",
        "pmid": "24196715",
        "pdb_id": null,
        "lead_author": "Tata et al. (Nature 2013)",
        "mechanism": "Facultative lineage plasticity: committed luminal secretory cells (SCGB1A1+) dedifferentiate into multipotent basal stem cells (KRT5+/TP63+) upon transient Notch inhibition.",
        "particle_diameter_nm": 50.0,
        "zeta_potential_mv": 0.0,
        "endosomal_escape_score": 0.92,
        "macrophage_stealth_score": 0.9,
        "cf_application": "Eliminates the requirement for crossing tight junctions: edit accessible apical club cells and pulse with a transient Notch inhibitor to repopulate the basal niche.",
        "bfi": 0.945,
        "feasibility_tier": "HIGH_FEASIBILITY",
        "transfer_domain": "epithelial_plasticity",
        "bfi_score": 0.945,
        "physical_barriers": "Basal niche inaccessibility; tight junction penetration requirement"
      },
      {
        "id": "CDI-002",
        "title": "Low-Affinity Transferrin Receptor (TfR1) Monovalent Transcytosis",
        "donor_field": "blood_brain_barrier",
        "primary_doi": "10.1126/scitranslmed.3002230",
        "pmid": "21613623",
        "pdb_id": "1CX8",
        "lead_author": "Yu et al. (Sci Transl Med 2011)",
        "mechanism": "Tuning ligand binding affinity (Kd = 200-400 nM) avoids lysosomal sorting, redirecting internalized vesicles to Rab11a exocytosis pathways across tight junctions.",
        "particle_diameter_nm": 55.0,
        "zeta_potential_mv": -1.0,
        "endosomal_escape_score": 0.9,
        "macrophage_stealth_score": 0.85,
        "cf_application": "Enables aerosolized nanoparticles to cross intact airway tight junctions via Rab11a-mediated basolateral exocytosis directly into the basal stem cell niche.",
        "bfi": 0.9125,
        "feasibility_tier": "HIGH_FEASIBILITY",
        "transfer_domain": "blood_brain_barrier",
        "bfi_score": 0.9125,
        "physical_barriers": "Epithelial tight junctions; endosomal/lysosomal degradation pathway"
      },
      {
        "id": "CDI-003",
        "title": "Polysarcosine (pSar) Biodegradable Stealth & Ester-Cleavable Ionizable Lipids",
        "donor_field": "mucosal_immunology",
        "primary_doi": "10.1016/j.bioactmat.2024.03.017",
        "pmid": "31960002",
        "pdb_id": null,
        "lead_author": "Siewert et al. (Biomaterials Sci 2020)",
        "mechanism": "Replaces immunogenic PEG conjugates with non-immunogenic polysarcosine (pSar); incorporates enzymatic ester cleavable aliphatic tails (macrophage t1/2 < 4h).",
        "particle_diameter_nm": 75.0,
        "zeta_potential_mv": 0.5,
        "endosomal_escape_score": 0.88,
        "macrophage_stealth_score": 0.98,
        "cf_application": "Abolishes the acute alveolar macrophage TLR7/8 cytokine storm (IL-8/TNF-alpha) and anti-PEG neutralizing antibody clearance that terminated VX-522.",
        "bfi": 0.9085,
        "feasibility_tier": "HIGH_FEASIBILITY",
        "transfer_domain": "mucosal_immunology",
        "bfi_score": 0.9085,
        "physical_barriers": "Polyanionic mucin adhesion; alveolar macrophage TLR7/8 activation and PEG clearance"
      },
      {
        "id": "CDI-001",
        "title": "CendR / NRP-1 Proteolytic Internalization & Mucinase Liquefaction",
        "donor_field": "solid_tumor_desmoplasia",
        "primary_doi": "10.3389/fonc.2013.00216",
        "pmid": "19962669",
        "pdb_id": "2QQM",
        "lead_author": "Sugahara et al. (Cancer Cell 2009)",
        "mechanism": "iRGD / C-end Rule peptide activation of Neuropilin-1 (NRP-1) macropinocytosis coupled with StcE mucin-cleaving protease (Malaker et al. PNAS 2019, DOI: 10.1073/pnas.1813020116).",
        "particle_diameter_nm": 65.0,
        "zeta_potential_mv": -2.5,
        "endosomal_escape_score": 0.85,
        "macrophage_stealth_score": 0.8,
        "cf_application": "Enzymatically liquefies thick CF sputum meshwork while actively triggering trans-epithelial penetration across apical ciliated and secretory cells.",
        "bfi": 0.86,
        "feasibility_tier": "HIGH_FEASIBILITY",
        "transfer_domain": "solid_tumor_desmoplasia",
        "bfi_score": 0.86,
        "physical_barriers": "Sputum mucin meshwork steric entrapment; apical endocytic barrier"
      },
      {
        "id": "CDI-005",
        "title": "Sendai Virus F/HN Pseudotyped Enveloped Delivery Vehicles (EDVs)",
        "donor_field": "synthetic_virology",
        "primary_doi": "10.1016/S2213-2600(15)00245-3",
        "pmid": "26149839",
        "pdb_id": "1Z4Z",
        "lead_author": "Alton et al. (Lancet Respir Med 2015)",
        "mechanism": "Hemagglutinin-neuraminidase (HN) binds apical sialic acid; fusion (F) protein mediates direct pH-independent membrane fusion at the apical plasma membrane.",
        "particle_diameter_nm": 95.0,
        "zeta_potential_mv": -4.0,
        "endosomal_escape_score": 0.99,
        "macrophage_stealth_score": 0.82,
        "cf_application": "Bypasses endosomal TLR pattern recognition entirely by directly injecting Cas9/prime-editor RNPs across the luminal membrane at neutral pH.",
        "bfi": 0.8353,
        "feasibility_tier": "MODERATE_FEASIBILITY",
        "transfer_domain": "synthetic_virology",
        "bfi_score": 0.8353,
        "physical_barriers": "Mucosal endosomal entrapment; lysosomal TLR pattern recognition"
      }
    ],
    "transcytosis_kinetics": [
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 10.0,
        "surface_binding_pct": 4.35,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 25.0,
        "surface_binding_pct": 10.2,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 50.0,
        "surface_binding_pct": 18.52,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 100.0,
        "surface_binding_pct": 31.25,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 200.0,
        "surface_binding_pct": 47.62,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 300.0,
        "surface_binding_pct": 57.69,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 500.0,
        "surface_binding_pct": 69.44,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "fcrn",
        "receptor_name": "Neonatal Fc Receptor (FcRn)",
        "pdb_id": "4N0F",
        "concentration_nm": 1000.0,
        "surface_binding_pct": 81.97,
        "internalized_pct": 92.67,
        "basolateral_exocytosis_pct": 76.33,
        "net_flux_pct_per_h": 38.165,
        "transcytosis_efficiency_pct": 82.85,
        "lysosomal_escape_pct": 84.36,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 10.0,
        "surface_binding_pct": 3.85,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 25.0,
        "surface_binding_pct": 9.09,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 50.0,
        "surface_binding_pct": 16.67,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 100.0,
        "surface_binding_pct": 28.57,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 200.0,
        "surface_binding_pct": 44.44,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 300.0,
        "surface_binding_pct": 54.55,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 500.0,
        "surface_binding_pct": 66.67,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "tfr",
        "receptor_name": "Transferrin Receptor 1 (TfR1)",
        "pdb_id": "1CX8",
        "concentration_nm": 1000.0,
        "surface_binding_pct": 80.0,
        "internalized_pct": 91.78,
        "basolateral_exocytosis_pct": 56.78,
        "net_flux_pct_per_h": 28.39,
        "transcytosis_efficiency_pct": 62.11,
        "lysosomal_escape_pct": 63.52,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 10.0,
        "surface_binding_pct": 3.12,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 25.0,
        "surface_binding_pct": 7.46,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 50.0,
        "surface_binding_pct": 13.89,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 100.0,
        "surface_binding_pct": 24.39,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 200.0,
        "surface_binding_pct": 39.22,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 300.0,
        "surface_binding_pct": 49.18,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 500.0,
        "surface_binding_pct": 61.73,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      },
      {
        "receptor_id": "pigr",
        "receptor_name": "Polymeric Immunoglobulin Receptor (pIgR)",
        "pdb_id": "5D4K",
        "concentration_nm": 1000.0,
        "surface_binding_pct": 76.34,
        "internalized_pct": 90.06,
        "basolateral_exocytosis_pct": 61.54,
        "net_flux_pct_per_h": 30.77,
        "transcytosis_efficiency_pct": 69.11,
        "lysosomal_escape_pct": 72.04,
        "verdict": "OPTIMAL_TRANSCYTOSIS"
      }
    ],
    "epithelial_trajectory": [
      {
        "day": 0,
        "uncorrected_secretory": 15.0,
        "corrected_secretory": 10.0,
        "transient_intermediate": 0.0,
        "corrected_basal_stem_cells": 0.0,
        "ciliated": 40.0,
        "cftr_plus_stem_cell_pct": 0.0
      },
      {
        "day": 1,
        "uncorrected_secretory": 11.695,
        "corrected_secretory": 7.532,
        "transient_intermediate": 3.812,
        "corrected_basal_stem_cells": 0.777,
        "ciliated": 40.075,
        "cftr_plus_stem_cell_pct": 2.59
      },
      {
        "day": 2,
        "uncorrected_secretory": 9.194,
        "corrected_secretory": 5.69,
        "transient_intermediate": 5.08,
        "corrected_basal_stem_cells": 1.882,
        "ciliated": 40.148,
        "cftr_plus_stem_cell_pct": 6.27
      },
      {
        "day": 3,
        "uncorrected_secretory": 7.297,
        "corrected_secretory": 4.318,
        "transient_intermediate": 5.135,
        "corrected_basal_stem_cells": 2.915,
        "ciliated": 40.221,
        "cftr_plus_stem_cell_pct": 9.72
      },
      {
        "day": 4,
        "uncorrected_secretory": 5.857,
        "corrected_secretory": 3.299,
        "transient_intermediate": 4.671,
        "corrected_basal_stem_cells": 3.759,
        "ciliated": 40.293,
        "cftr_plus_stem_cell_pct": 12.53
      },
      {
        "day": 5,
        "uncorrected_secretory": 4.764,
        "corrected_secretory": 2.541,
        "transient_intermediate": 4.037,
        "corrected_basal_stem_cells": 4.409,
        "ciliated": 40.364,
        "cftr_plus_stem_cell_pct": 14.7
      },
      {
        "day": 6,
        "uncorrected_secretory": 4.47,
        "corrected_secretory": 2.256,
        "transient_intermediate": 2.784,
        "corrected_basal_stem_cells": 4.862,
        "ciliated": 40.435,
        "cftr_plus_stem_cell_pct": 16.21
      },
      {
        "day": 7,
        "uncorrected_secretory": 4.762,
        "corrected_secretory": 2.292,
        "transient_intermediate": 1.566,
        "corrected_basal_stem_cells": 5.105,
        "ciliated": 40.504,
        "cftr_plus_stem_cell_pct": 17.02
      },
      {
        "day": 8,
        "uncorrected_secretory": 5.047,
        "corrected_secretory": 2.329,
        "transient_intermediate": 0.881,
        "corrected_basal_stem_cells": 5.238,
        "ciliated": 40.573,
        "cftr_plus_stem_cell_pct": 17.46
      },
      {
        "day": 9,
        "uncorrected_secretory": 5.326,
        "corrected_secretory": 2.368,
        "transient_intermediate": 0.496,
        "corrected_basal_stem_cells": 5.312,
        "ciliated": 40.641,
        "cftr_plus_stem_cell_pct": 17.71
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