TISSUE-BASED SMALL ANIMAL MODEL FOR HIV DRUG DISCOVERY

用于艾滋病毒药物发现的基于组织的小动物模型

• 批准号: 6348654
• 负责人: Cheryl Stoddart
• 金额: $ 97.07万
• 依托单位: J. DAVID GLADSTONE INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348654
• 关键词: SCID mouse; antiAIDS agent; biological models; drug discovery /isolation; drug screening /evaluation; model design /development

The National Institute of Allergy and Infectious Diseases (NIAID) supports a comprehensive portfolio of contract resources to discover and develop novel therapeutic agents for the prevention and treatment of infections caused by Human Immunodeficiency Virus-1 (HIV-1), AIDS-associated opportunistic pathogens, and other infectious agents. Animal model resources constitute one element of this drug discovery and development program. The purpose of the present project is to provide a resource for evaluating potential therapeutics for HIV-1 infection. Details regarding access by the scientific community are provided at: http://www.niaid.nih.gov/daids/pdatguide/overview.htm The contractor is responsible for i) evaluating therapeutic agents, alone and in combination, for efficacy and toxicity in vitro and in the SCID-hu thymus/liver animal model; ii) performing quality assurance/control of the components of the in vitro and in vivo assay systems, to insure reproducible evaluation of candidate therapies; iii) determining optimal routes and schedules of administration; iv) modifying the model system as necessary, to augment its usefulness for evaluating potential HIV-1 therapeutics; and 5) preparing and submitting periodic and interim reports.

国家过敏和传染病研究所（NIAID）支持合同资源的全面组合，以发现和开发用于预防和治疗人类免疫缺陷病毒-1（HIV-1），艾滋病相关机会病原体和其他传染性病原体引起的感染的新型治疗剂。 动物模型资源构成该药物发现和开发计划的一个要素。 本项目的目的是为评估HIV-1感染的潜在治疗方法提供资源。 关于科学界获取信息的详细情况，见： http://www.niaid.nih.gov/daids/pdatguide/overview.htm 承包商负责：i）在体外和SCID-hu胸腺/肝脏动物模型中评价单独和联合治疗剂的疗效和毒性; ii）对体外和体内试验系统的组成部分进行质量保证/控制，以确保候选疗法的可重复评价; iii）确定最佳给药途径和时间表; iv）必要时修改模型系统，以增加其用于评估潜在的HIV-1治疗剂的有用性;和5）准备和提交定期和中期报告。

项目成果

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

• DOI: 10.1371/journal.pone.0000655
• 发表时间: 2007-08-01
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Stoddart CA;Bales CA;Bare JC;Chkhenkeli G;Galkina SA;Kinkade AN;Moreno ME;Rivera JM;Ronquillo RE;Sloan B;Black PL
• 通讯作者: Black PL

Human immunodeficiency virus type 1 Nef-mediated downregulation of CD4 correlates with Nef enhancement of viral pathogenesis.

人类免疫缺陷病毒 1 型 Nef 介导的 CD4 下调与 Nef 增强病毒发病机制相关。

• DOI: 10.1128/jvi.77.3.2124-2133.2003
• 发表时间: 2003
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Stoddart,CherylA;Geleziunas,Romas;Ferrell,Sharon;Linquist-Stepps,Valerie;Moreno,MaryE;Bare,Christopher;Xu,Weiduan;Yonemoto,Wes;Bresnahan,PatriciaA;McCune,JosephM;Greene,WarnerC
• 通讯作者: Greene,WarnerC

Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice.

白蛋白偶联的C34肽HIV-1融合抑制剂：C34和T-20的均衡性，在SCID-HU THY/LIV小鼠中具有持续的活性。

• DOI: 10.1074/jbc.m805536200
• 发表时间: 2008-12-05
• 期刊: The Journal of biological chemistry
• 作者: Stoddart CA;Nault G;Galkina SA;Thibaudeau K;Bakis P;Bousquet-Gagnon N;Robitaille M;Bellomo M;Paradis V;Liscourt P;Lobach A;Rivard ME;Ptak RG;Mankowski MK;Bridon D;Quraishi O
• 通讯作者: Quraishi O

Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice.

HIV-1成熟抑制剂bevirimat在scid-hu/liv小鼠中的有效活性。

• DOI: 10.1371/journal.pone.0001251
• 发表时间: 2007-11-28
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Stoddart CA;Joshi P;Sloan B;Bare JC;Smith PC;Allaway GP;Wild CT;Martin DE
• 通讯作者: Martin DE