Nuclease-Resistant Aptamers to Botox and Anthrax Toxins
肉毒杆菌和炭疽毒素的核酸酶抗性适体
基本信息
- 批准号:6736672
- 负责人:
- 金额:$ 9.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-04-15 至 2004-10-14
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by investigator):
Botulinum toxin and anthrax are two likely bioweapons of choice in military attacks or terrorism against the United States. As such, effective post-exposure therapies, such as antitoxins, to both agents are required. Operational Technologies (OpTech) has extensive experience in the area of DNA aptamer development for the detection of biowarfare agents and biotoxins via its Senior Scientist. OpTech proposes to team with Prof. James Chambers of the Biochemistry Department at the University of Texas at San Antonio (UTSA). Together, the OpTech-UTSA team will develop 2'-pyrimidine modified nuclease-resistant "shielded" DNA aptamers by the SELEX process to botulinum toxin (BOTOX) and the three anthrax toxin components (edema factor, lethal factor, and protective antigen). "Shielded aptamers" are well suited to eventual in vivo therapeutic use and would be of low immunogenicity. In Phase I, OpTech will generate shielded aptamers to several serotypes (at least A, B and E) of BOTOX and will determine their relative binding affinities for the intact "derivative" toxin as well as the separate heavy (100 kD) and light 50 kD) chains. In Phase II, OpTech will develop and test anti-anthrax toxin component shielded aptamers as well as clone and sequence all promising aptamers reactive against either toxin family.
Development of "shielded" (nuclease-resistant) aptamers as toxin inhibitors with greater affinity than antibodies or other antidotes, in general, guarantees the owner of the technology entry into a growing biodefense market. If successful in this project, OpTech will use the knowledge gained to develop improved inhibitors of other bacterial toxins, such as cholera toxin, as well as snake and spider venoms. The therapeutic market for such products would be immense, because DNA is nontoxic and hypoallergenic (does not induce a significant immune response), thus avoiding "serum sickness" or anaphylaxis upon secondary use. Such reagents could also be used in environmental biosensors or diagnostic test kits for detection of BOTOX and anthrax toxins in body fluids or environmental samples.
描述(由研究者提供):
肉毒杆菌毒素和炭疽是两种可能的生物武器的选择,在军事攻击或恐怖主义对美国。因此,需要对这两种药物进行有效的暴露后治疗,如抗毒素。Operational Technologies(OpTech)在DNA适体开发领域拥有丰富的经验,通过其高级科学家检测生物战剂和生物毒素。OpTech建议与德克萨斯大学圣安东尼奥分校(UTSA)生物化学系的James Chambers教授合作。OpTech-UTSA团队将通过针对肉毒杆菌毒素(BOTOX)和三种炭疽毒素组分(水肿因子、致死因子和保护性抗原)的SELEX过程,共同开发2 '-嘧啶修饰的抗核酸酶“屏蔽”DNA适体。“屏蔽适体”非常适合于最终的体内治疗用途,并且具有低免疫原性。在I期,OpTech将产生针对BOTOX的几种血清型(至少A、B和E)的屏蔽适体,并将确定它们对完整“衍生”毒素以及单独的重链(100 kD)和轻链(50 kD)的相对结合亲和力。在第二阶段,OpTech将开发和测试抗炭疽毒素成分屏蔽适体,以及克隆和测序所有有前途的适体对任何毒素家族的反应。
一般来说,开发“屏蔽”(抗核酸酶)适体作为比抗体或其他解毒剂具有更大亲和力的毒素抑制剂,保证了技术所有者进入不断增长的生物防御市场。如果该项目取得成功,OpTech将利用所获得的知识开发其他细菌毒素的改进抑制剂,如霍乱毒素以及蛇和蜘蛛毒液。这种产品的治疗市场将是巨大的,因为DNA是无毒的和低过敏性的(不诱导显著的免疫反应),从而避免了“血清病”或二次使用时的过敏反应。这些试剂还可用于环境生物传感器或诊断测试试剂盒,用于检测体液或环境样品中的肉毒杆菌毒素和炭疽毒素。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Aptamer selection express: a novel method for rapid single-step selection and sensing of aptamers.
- DOI:
- 发表时间:2008-12
- 期刊:
- 影响因子:0
- 作者:Maomian Fan;Shelly Roper McBurnett;C. Andrews;A. Allman;J. Bruno;J. Kiel
- 通讯作者:Maomian Fan;Shelly Roper McBurnett;C. Andrews;A. Allman;J. Bruno;J. Kiel
A review of therapeutic aptamer conjugates with emphasis on new approaches.
- DOI:10.3390/ph6030340
- 发表时间:2013-03-19
- 期刊:
- 影响因子:0
- 作者:Bruno JG
- 通讯作者:Bruno JG
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John G Bruno其他文献
John G Bruno的其他文献
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{{ truncateString('John G Bruno', 18)}}的其他基金
Development of Anti-OLAM Aptamers as Novel Analgesics (Phase 2)
开发抗 OLAM 适体作为新型镇痛药(第 2 阶段)
- 批准号:
9059113 - 财政年份:2012
- 资助金额:
$ 9.99万 - 项目类别:
Development of Anti-OLAM Aptamers as Novel Analgesics
抗 OLAM 适体作为新型镇痛药的开发
- 批准号:
8306470 - 财政年份:2012
- 资助金额:
$ 9.99万 - 项目类别:
Nuclease-Resistant Aptamers for Anthrax Opsonization
用于炭疽调理作用的核酸酶抗性适体
- 批准号:
6735824 - 财政年份:2004
- 资助金额:
$ 9.99万 - 项目类别:
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