{
  "abstract": "CRISPR gene editing offers unprecedented genomic and transcriptomic control, positioning it as a powerful tool for cell therapies. Non-viral CRISPR delivery avoids the immunogenicity, genomic integration, and packaging limits of viral vectors, but local or systemic injections of non-viral nanoparticles suffers from transient action and poor biodistribution. Alternatively, biomaterial-based delivery improves nanoparticle localization and sustains delivery, yet current approaches rely on non-specific adsorption of nanoparticles to scaffolds, risking aggregation, destabilization, and unreliable release kinetics. This work establishes a novel strategy to covalently tether nanoparticles to biomaterial substrates through SnoopTag and SpyTag bioconjugation systems for spatiotemporal control of non-viral CRISPR delivery. The RALA cell-penetrating peptide, an efficient and low-cytotoxicity CRISPR delivery system, was functionalized with SnoopTag without altering nanoparticle formation or transfection capacity. SnoopTag-functionalized nanoparticles were then covalently tethered to SpyTag-decorated zwitterionic microgels via a SnoopCatcher-SpyCatcher fusion protein. This platform achieves sustained RALA-mRNA nanoparticle delivery and prolonged CRISPR activation in human mesenchymal stem cells seeded within CRISPR-loaded microgel scaffolds. This work establishes a defined biorthogonal conjugation system that tethers non-viral nanoparticles to biomaterial platforms for sustained and localized CRISPR gene editing.",
  "abstract_shown": true,
  "affiliations": [
    "Lehigh University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "J. P. Graham"
    },
    {
      "name": "E. E. Wheeler"
    },
    {
      "name": "K. J. Leach"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Gonzalez-Fernandez"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7nbjzrx7s606g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.751510",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.751510v1.full",
  "id": "7nbjzrx7s606g",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.751510v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioengineering"
    ],
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7214013339",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.751510v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7nbjzrx7s606g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:47Z",
      "native_id": "10.64898/2026.09.18.751510",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.18.751510v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Spatiotemporal Control of Genetic and Epigenetic Editing through Covalent Tethering of CRISPR Nanoparticles to Zwitterionic Microgels",
  "title_text": "Spatiotemporal Control of Genetic and Epigenetic Editing through Covalent Tethering of CRISPR Nanoparticles to Zwitterionic Microgels",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:47Z",
  "url": "https://research.draconitic.com/paper/7nbjzrx7s606g",
  "venue": "bioRxiv",
  "versions": []
}