基因治疗安全性评价的GLP困境与革新路径

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GLPDilemmas and Innovative Approaches in Safety Evaluation of Gene Therapy

LUO Jie (Shanghai WakerBioscience Co.,Ltd.)

Abstract: Celland gene therapy(CGT),asanewgenerationof precision therapies,demonstrates immense potential in treatingcancers,rarediseases,andgeneticdisorders.However,itsvigorousdevelopmentimposes higherdemandsonfety evaluation.Particularlyforgene therapyproducts utilizing integrating vectors,thesafety assessmentofIntegration Sites (IS)is criticallycomplexasitisdirectlyrelatedtogenotoxicityandtumorgenicisk.Currentlyonductingevaluatiosin compliance with GoodLaboratoryPractice (GLP)isintermationallyrecognizedas thesafeguard.Nevertheless,traditional GLP systems andtheir guiding principles primarily focus on methodologies for invivo animal studies.This paper critically analyzes the key limitations ofthe GLP system when applied toCGTIS evaluation: the difcultyofrapidly evolving detectionmethods meting GLP'sstringentvalidationrequirements;andtheIS hascomplex biological significanceand its risks maybedelayed,whichdoes notmatch thetraditional GLPevaluationmodelrelying onquantifiable toxicityendpoints andfixedobservationperiods.The study pointsoutthat existing GLPtesting frameworks lack specificcontentandtechnical guidancededicatedtoIS evaluation,highlightingthe tensionbetweentheadvancementofregulatoryscienceandtherelative conservatismofthe GLPsystem.To addressthese challenges,thepaperproposes that future efortsshouldfocus onrevising GLP guielines to incorporate CGT-specificcharacteristics,developing novel quality assrance strategies,and advancing precision medicine.

Keywords:cell and gene therapy(CGT); Good Laboratory Practice (GLP),Insertion Site SafetyAssessment (IS evaluation)

0 引言

细胞与基因治疗（CellandGene Therapy，CGT）作为新一代精准疗法，正深刻变革生物医药领域，尤其在肿瘤、罕见病及遗传病的治疗中展现出巨大潜力。（剩余7641字）