Rapid Transient Depletion of Pre-existing Antibodies for rAAV Gene Delivery
快速瞬时消耗 rAAV 基因传递的现有抗体
基本信息
- 批准号:9807279
- 负责人:
- 金额:$ 23.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-12 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntibodiesAntibody SuppressionBlocking AntibodiesBrainCaspaseCellsChildCleaved cellClinicDataDependovirusDevelopmentDiseaseDoseDose-LimitingEnzymesExcisionGene DeliveryGoalsHalf-LifeHigh PrevalenceHistopathologyHumanImmune TargetingImmunoglobulin GImmunosuppressionIndividualInjectionsLysosomal Storage DiseasesMediatingModelingMucopolysaccharidosis III BMusNeuropathyPathologyPatientsPeripheralPopulationPublishingRecombinant adeno-associated virus (rAAV)RegimenSirolimusStreptococcusTestingTherapeuticTissuesToxic effectTranslationsViral GenesViral Vectoradeno-associated viral vectorbaseclinical applicationclinically relevantexperimental studygene therapymouse modelnovelnovel strategiesprednisolonetoolvectorvector biodistribution
项目摘要
Project Summary:
This proposal targets a critical challenge in the translation of AAV-mediated gene therapy, the widespread
pre-existing αAAV antibodies (Abs) in humans. Pre-existing αAAV-Abs block AAV vectors from entering and
transducing target cells. Currently, only αAAV-Abs-negative individuals are eligible for AAV-gene therapy
treatment, because no effective approach is available to overcome this challenge. Our recently published
studies demonstrated that broad immune targeting is required for effective Ab-depletion by immune
suppression (IS) and identified an effective IS Ab-depletion approach in a mouse model, using combination
of rapamycin and prednisolone. However, this IS regimen requires up to 8-12-week-long daily administration.
The IgG degrading enzymes of Streptococci (IdeS) are cysteine proteases that specifically cleaves IgG
molecules. Numerous studies have demonstrated rapid and effective IgG degradation by IdeS in animals and
in humans, supporting the therapeutic potential of IdeS. IdeS has a short half-life of 4.9±2.8hr with no
demonstrated dose limiting toxicity. We therefore hypothesize that IV IdeS administration may offer a novel
tool to overcome the pre-existing αAAV-IgG for rAAV-mediated gene therapy. This proposal is to develop a
novel effective ab-depletion approach for the effective translation of rAAV gene therapy to treat diseases in
clinic, using a mouse model of MPS IIIB, a devastating neuropathic lysosomal storage disease, for which not
treatment is currently available. Taking advantage of demonstrated rapid effective Ab removal by IdeS, this
proposal will lead to the development of a novel approach for effective depletion of pre-existing αAAV-Abs,
which may make all patients in need eligible to AAV gene therapy, and viral gene therapy in general. We
therefore believe that IdeS may offer the answer to the challenge posed by pre-existing Abs to the translation
of gene therapy products using AAV and other viral vectors.
项目总结:
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
HAIYAN FU其他文献
HAIYAN FU的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('HAIYAN FU', 18)}}的其他基金
Develop AAV9 gene replacement therapy for treating MPS I
开发 AAV9 基因替代疗法治疗 MPS I
- 批准号:
10545520 - 财政年份:2022
- 资助金额:
$ 23.33万 - 项目类别:
Develop AAV9 gene replacement therapy for treating MPS I
开发 AAV9 基因替代疗法治疗 MPS I
- 批准号:
10674027 - 财政年份:2022
- 资助金额:
$ 23.33万 - 项目类别:
Development of gene therapy product for treating MPS IIIB
开发治疗 MPS IIIB 的基因治疗产品
- 批准号:
10006261 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Facilitate by-stander effects by EV-mRNA cargo in AAV gene therapy for MPS IIIC
在 MPS IIIC 的 AAV 基因治疗中通过 EV-mRNA 货物促进旁观者效应
- 批准号:
10040153 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
PATTERNS OF r AAV VECTOR INSERTION ASSOCIATED WITH LIVER TUMORS IN A MOUSE MODEL
小鼠模型中与肝肿瘤相关的 r AAV 载体插入模式
- 批准号:
9269161 - 财政年份:2013
- 资助金额:
$ 23.33万 - 项目类别:
CNS Gene Therapy for Mucopolysaccharidosis IIIB w/ AAV
使用 AAV 治疗粘多糖贮积症 IIIB 的中枢神经系统基因疗法
- 批准号:
6640419 - 财政年份:2002
- 资助金额:
$ 23.33万 - 项目类别:
CNS Gene Therapy for Mucopolysaccharidosis IIIB w/ AAV
使用 AAV 治疗粘多糖贮积症 IIIB 的中枢神经系统基因疗法
- 批准号:
6547921 - 财政年份:2002
- 资助金额:
$ 23.33万 - 项目类别:
CNS Gene Therapy for Mucopolysaccharidosis IIIB w/ AAV
使用 AAV 治疗粘多糖贮积症 IIIB 的中枢神经系统基因疗法
- 批准号:
6768655 - 财政年份:2002
- 资助金额:
$ 23.33万 - 项目类别:
CNS Gene Therapy for Mucopolysaccharidosis IIIB w/ AAV
使用 AAV 治疗粘多糖贮积症 IIIB 的中枢神经系统基因疗法
- 批准号:
7030557 - 财政年份:2002
- 资助金额:
$ 23.33万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 23.33万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 23.33万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 23.33万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 23.33万 - 项目类别:
Research Grant
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别:
Grant for R&D
PLA2G2D Antibodies for Cancer Immunotherapy
用于癌症免疫治疗的 PLA2G2D 抗体
- 批准号:
10699504 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别:
Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
- 批准号:
10491642 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别:
Novel Immunogens to Elicit Broadly Cross-reactive Antibodies That Target the Hemagglutinin Head Trimer Interface
新型免疫原可引发针对血凝素头三聚体界面的广泛交叉反应抗体
- 批准号:
10782567 - 财政年份:2023
- 资助金额:
$ 23.33万 - 项目类别: