CAPTIS DIAGNOSTICS - SBIR CONCEPT AWARD - DEVELOPMENT OF NON-INVASIVE ASSAY FOR MOLECULAR CHARACTERIZATION OF PEDIATRIC LOW-GRADE GLIOMA

目前儿科低级别胶质瘤（pLGG）的分子表征面临重大挑战：(1)金标准组织活检具有侵入性，往往不适合pLGG的诊断和重复监测；(2)组织活检无法捕获整个肿瘤内存在的异质性。该建议的长期目标是通过开发范式转换诊断工具来减轻儿童中枢神经系统（CNS）肿瘤的负担。为了克服这些挑战，本研究建议开发首个基于非侵入性细胞外囊泡（EV）的pLGG诊断方法，其具体目标有两个：(1)开发基于纳米材料的CNS-EV选择性分离技术；(2)验证纳米材料技术在pLGG无创分子表征中的应用。将采用双管齐下的方法来实现里程碑：(1)优化基于纳米材料的技术，从等离子体中富集cns - ev；(2)从pLGG患者血浆中分离纳米材料cns -EV检测具有临床意义的EV核酸突变。该SBIR将产生(1)基于纳米材料的CNS-EV分离试剂盒；(2)基于pLGG血浆的非侵入性纳米材料技术的概念验证，该技术已准备好进行大规模临床验证。与金标准方法侵入性组织活检相比，提出的非侵入性技术有望为pLGG的治疗和管理提供范式转变。

Current molecular characterization of pediatric low-grade glioma (pLGG) face significant challenges: (1) the gold standard tissue biopsy is invasive and often unfit for pLGG diagnosis and repetitive monitoring; (2) tissue biopsy is unable to capture the heterogeneity present within the entire tumor. The long-term goal of this proposal is to reduce the burden of pediatric central nervous system (CNS) tumors through developing paradigm shifting diagnostic tools. This proposal proposes to overcome these challenges by developing the first non-invasive extracellular vesicle (EV)-based assay for pLGG diagnosis with two specific aims: (1) developing nanomaterial-based technology for selective isolation of CNS-EV; (2) validate the nanomaterial-based technology in non-invasive molecular characterization of pLGG. Two-pronged approach will be used to achieve the milestones: (1) nanomaterial-based technology will be optimized to enrich CNS-EVs from plasma; (2) detecting clinically significant EV nucleic acid mutation from nanomaterial-isolated CNS-EVs from plasma of pLGG. This SBIR will result in (1) a nanomaterial-based kit for CNS-EV isolation; (2) proof-of-concept validation of non-invasive nanomaterial-based technology with pLGG plasma, which is ready for large clinical validation. Compared with the gold standard method invasive tissue biopsy, the proposed non-invasive technology is expected to provide a paradigm shift in the treatment and management of pLGG.