开发用于长期表达 eCD4-Ig 的 AAV 载体-猫眼课题宝

开发用于长期表达 eCD4-Ig 的 AAV 载体

批准号：

9770769

负责人：

MICHAEL DAVID ALPERT

金额：

$99.97万

依托单位：

EMMUNE, INC

依托单位国家：

美国

项目类别：

财政年份：

2017

资助国家：

美国

项目状态：

已结题

起止时间：

2017-08-01 至 2021-07-31

来源：

https://reporter.nih.gov/project-details/9770769

关键词：

Affinity Antibodies Antibody Formation Antibody Response Antigen-Presenting Cells Antiviral Agents Binding CCR5 gene CMV promoter Dependovirus Development Dose Engineering Enhancers Enzymes Epitopes Exhibits Gene Expression Glycoproteins Grant HIV HIV-1 Healthcare Systems Human T-lymphotropic virus 1 Immune response Immunoglobulin Constant Region Immunoglobulin Somatic Hypermutation Immunologics In Vitro Infection Innate Immune Response Internal Ribosome Entry Site Intramuscular Injections Intravenous Introns Laboratory Animals Life Longevity Macaca Macaca mulatta Methylation Muscle Muscle Cells Nature Patients Peptide Hydrolases Plasma Polyadenylation Post-Translational Protein Processing Primates Production Research Risk Simian virus 40 Site Structure T cell response Testing Time Transgenes Viral Virus Receptors adeno-associated viral vector base cellular transduction cost design expression vector fitness gene transfer vector global health immunogenic immunogenicity improved innovation neutralizing antibody novel pandemic disease peptidomimetics prevent promoter protein-tyrosine sulfotransferase 2 public health relevance receptor simian human immunodeficiency virus synthetic antibodies transcription factor transgene expression vector vector genome

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中文摘要

翻译

摘要/摘要/项目描述单次肌肉注射表达eCD4-Ig的腺相关病毒(AAV)载体具有有可能终生治疗或预防艾滋病毒-1感染。ECD4-Ig是一种合成抗体或“免疫粘附素” 通过将部分病毒受体(CD4)和辅助受体(CCR5)融合到AFP的恒定区构建而成抗体。因为eCD4-Ig与HIV-1包膜糖蛋白(Env)通过与为了识别其受体和辅助受体，eCD4-Ig中和了100%的HIV-1分离株并呈现病毒逃脱的基本障碍。我们之前已经证明，接种了AAV的恒河猴表达eCD4-Ig对大剂量静脉注射猴-免疫球蛋白具有灭菌保护作用。人类免疫缺陷病毒(SIV)。现在，我们提出了几项实用的创新，旨在最大限度地通过AAV转导的肌肉长期维持的血浆中eCD4-Ig的浓度。

英文摘要

ABSTRACT / SUMMARY / PROJECT DESCRIPTION A single intramuscular injection of an adeno-associated virus (AAV) vector that expresses eCD4-Ig has the potential to treat or prevent HIV-1 infection for a lifetime. eCD4-Ig is a synthetic antibody or “immunoadhesin” constructed by fusing parts of the viral receptor (CD4) and coreceptor (CCR5) to the constant region of an antibody. Because eCD4-Ig binds the HIV-1 envelope glycoprotein (Env) through the same contacts used by Env to recognize its receptor and coreceptor, eCD4-Ig neutralizes 100% of HIV-1 isolates and presents fundamental barriers to viral escape. We have previously shown that rhesus macaques inoculated with AAV expressing eCD4-Ig exhibited sterilizing protection against high-dose intravenous challenges with simian- human immunodeficiency virus (SHIV). Now, we propose several practical innovations designed to maximize the concentrations of eCD4-Ig in plasma that are sustained over the long term by AAV-transduced muscle.

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