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Current therapies targeting this pathway are effective but require lifelong administration, underscoring the need for durable and potentially curative interventions. Adenine base editors (ABEs), engineered from CRISPR\/Cas systems, enable precise single\u2010nucleotide modifications with minimal genomic disruption, offering a promising strategy for long\u2010term gene silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NG\u2010ABE8e was delivered via AAV8 or lipid nanoparticles (LNP) to disrupt the exon 2 splice donor site of\n                      <jats:italic>Klkb1<\/jats:italic>\n                      in\n                      <jats:italic>Serping1<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice. Editing outcomes were quantified by high\u2010throughput sequencing; serum kallikrein levels were measured by ELISA; and vascular permeability was evaluated using Evans blue dye extravasation, fluorescent tracer leakage, and VE\u2010cadherin immunostaining. Safety evaluations included off\u2010target analysis, histopathology, serum biochemistry, activated partial thromboplastin time (aPTT), and systemic hemodynamic stability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AAV8\u2010NG\u2010ABE8e induced &gt;\u200960% A\u2022T\u2010to\u2010G\u2022C conversion at the target site, promoting exon 2 skipping and reducing\n                      <jats:italic>Klkb1<\/jats:italic>\n                      mRNA and serum kallikrein levels by &gt;\u200985%, an effect sustained for at least 1\u2009year. AAV8\u2010NG\u2010ABE8e also reversed bradykinin\u2010driven vascular hyperpermeability and attenuated inflammatory gene signatures. Prolongation of aPTT was observed only when circulating kallikrein levels declined below 2\u2009\u03bcg\/mL. Similarly, LNP\u2010mediated delivery of NG\u2010ABE8e mRNA resulted in &gt;\u200990% reductions in\n                      <jats:italic>Klkb1<\/jats:italic>\n                      expression and serum kallikrein levels. No evidence of significant long\u2010term toxicity was detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that, in a murine model, NG\u2010ABE8e\u2013mediated disruption of\n                      <jats:italic>Klkb1<\/jats:italic>\n                      enables durable suppression of serum kallikrein and vascular stabilization, suggesting its potential as a promising single\u2010intervention strategy for the treatment of HAE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70152","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T15:32:18Z","timestamp":1763134338000},"page":"1720-1734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long\u2010Term 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