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While CRISPR\u2010based editing is well\u2010established for small genetic modifications, large insert knock\u2010in remains a technical bottleneck. This review examines current strategies for achieving efficient, precise and safe integration of large genetic elements. We compare delivery methods for CRISPR components, highlighting electroporation of Cas9 ribonucleoproteins as the most efficient but often cytotoxic approach; emerging alternatives such as cell\u2010penetrating peptides and lipid nanoparticles offer improved cell viability at the expense of editing efficiency. The influence of genomic locus selection, guide RNA design and chromatin context on editing outcomes, as well as the role of homology\u2010directed repair (HDR) template design is evaluated. Various template formats\u2014including linear double\u2010 and single\u2010stranded DNA, plasmids, circular single\u2010stranded (css) DNA and recombinant adeno\u2010associated virus (rAAV)\u2014are assessed for their efficiency, toxicity and risk of off\u2010target integration. Where possible, cross\u2010study normalisation is used to enable meaningful comparisons. rAAV templates consistently achieve the highest insertion rates but come with concerns regarding cost, size limitations and insertional mutagenesis, whereas non\u2010viral approaches such as cssDNA templates show promise. Additionally, we review the use of small\u2010molecule modulators to enhance HDR efficiency, noting trade\u2010offs between improved insertion rates and potential genomic instability. Overall, successful large insert editing requires balancing of editing efficiency, cell viability and genomic safety considerations. Continued optimisation of delivery systems, template design and repair pathway modulation will be critical for advancing scalable and clinically viable T\u2010cell therapies.\n                  <\/jats:p>","DOI":"10.1002\/cti2.70124","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:35:13Z","timestamp":1792373713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From delivery to integration:\n                    <scp>CRISPR<\/scp>\n                    \u2010mediated large insert gene editing in primary human T\u00a0cells"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0320-8569","authenticated-orcid":false,"given":"Ben","family":"Buttle","sequence":"first","affiliation":[{"name":"School of Biological Sciences The University of Auckland  Auckland New 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