Antisense inhibitors for enhanced plasmid production

用于增强质粒生产的反义抑制剂

基本信息

  • 批准号:
    6883528
  • 负责人:
  • 金额:
    $ 13.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-06-01 至 2006-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Large scale manufacture of plasmid DNA is becoming increasingly important as the next generation of biotechnology products (gene medicines and DNA vaccines) make their way into clinical trials, and eventually into the pharmaceutical marketplace. Although extensive research on plasmid DNA purification methodologies has resulted in efficient purification processes, plasmid DNA production capacity is severely limited by low fermentation yield. The hypothesis of the proposed work is that E. coli plasmid DNA can be more efficiently produced by co-expression of an antisense RNA targeting the ColEI origin represser RNA (RNAI). The strategy will be to make designer antisense RNAI inhibitors, inducing them at the appropriate time to allow runaway replication of target plasmids. In Specific Aim 1, we will construct recombinant plasmids for expression of RNAI inhibitors. In Specific Aim 2, we will screen for antisense RNAI inhibitors useful for the production of plasmids. The overall goal of the proposed feasibility study is to determine whether such a bacterial strain is a significant advantage in the production of plasmid DNA using existing replicons (milestone I). If successful, Phase II studies will include: 1) improved constructs for insertion of the antisense RNA into the E. coli chromosome; 2) creating the strains needed and 3) fermentation process development. In Phase III, NTC will introduce the improved strains into commercial plasmid production. Potential commercial applications Success in constructing one or more useful strains of bacteria expressing RNAI inhibitor in a controllable fashion (milestone II) will help to overcome a major obstacle in the economical production of highly purified plasmid DNA for use in human Pharmaceuticals and DNA vaccines. Such strains will be rapidly introduced into Nature Technology's large scale DNA manufacturing process, and will also be made available for licensing to commercial users through the company's technology transfer and licensing program. Currently, experimental gene drugs and DNA vaccines are routinely made on the gram scale, mostly for use in animal safety and efficacy studies. However, the advent of FDA approved commercial products will require scaling up to kilograms, for example, for a widely used vaccine. Judging from the current price of $22,000- $46,000/gram of DNA produced, a less costly, scalable fermentation process is badly needed. The economic benefits and potential market size for the resulting products can be readily appreciated. The likelihood of a commercially useful and valuable product resulting from the proposed work is considered high.
描述(由申请人提供):随着下一代生物技术产品(基因药物和DNA疫苗)进入临床试验并最终进入制药市场,质粒DNA的大规模生产变得越来越重要。尽管对质粒DNA纯化方法的广泛研究已经产生了高效的纯化工艺,但质粒DNA的生产能力受到低发酵产率的严重限制。本工作的假设是E.通过共表达靶向ColEI起始阻遏物RNA(RNAi)的反义RNA,可以更有效地产生大肠杆菌质粒DNA。该策略将是制造设计的反义RNAi抑制剂,在适当的时间诱导它们以允许靶质粒的失控复制。在具体目标1中,我们将构建用于表达RNAi抑制剂的重组质粒。在具体目标2中,我们将筛选用于质粒生产的反义RNAi抑制剂。拟议可行性研究的总体目标是确定这种细菌菌株在使用现有复制子生产质粒DNA方面是否具有显著优势(里程碑I)。如果成功的话,II期研究将包括:1)将反义RNA插入E.大肠杆菌染色体; 2)创建所需菌株和3)发酵工艺开发。在第三阶段,NTC将把改进的菌株引入商业质粒生产。 潜在的商业应用 成功构建一种或多种以可控方式表达RNAi抑制剂的有用细菌菌株(里程碑II)将有助于克服经济生产用于人类药物和DNA疫苗的高度纯化质粒DNA的主要障碍。这些菌株将被迅速引入自然技术公司的大规模DNA制造过程,并将通过该公司的技术转让和许可计划向商业用户提供许可。目前,实验性基因药物和DNA疫苗通常以克为单位生产,主要用于动物安全性和有效性研究。然而,FDA批准的商业产品的出现将需要扩大到千克,例如,对于广泛使用的疫苗。从目前每克DNA生产22,000 - 46,000美元的价格来看,迫切需要一种成本更低、可扩展的发酵工艺。由此产生的产品的经济效益和潜在市场规模是显而易见的。从拟议的工作中产生商业上有用和有价值的产品的可能性被认为很高。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system.
  • DOI:
    10.1016/j.vaccine.2009.06.017
  • 发表时间:
    2009-10-30
  • 期刊:
  • 影响因子:
    5.5
  • 作者:
    Luke J;Carnes AE;Hodgson CP;Williams JA
  • 通讯作者:
    Williams JA
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James Williams其他文献

James Williams的其他文献

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{{ truncateString('James Williams', 18)}}的其他基金

MiniPlasmid vector platform for non-viral gene therapy
用于非病毒基因治疗的 MiniPlasmid 载体平台
  • 批准号:
    8512989
  • 财政年份:
    2013
  • 资助金额:
    $ 13.62万
  • 项目类别:
eukaryotic expression vectors resistant to transgene silencing
抗转基因沉默的真核表达载体
  • 批准号:
    8057175
  • 财政年份:
    2007
  • 资助金额:
    $ 13.62万
  • 项目类别:
Rapid deployment DNA vaccine for pandemic influenza
快速部署大流行性流感 DNA 疫苗
  • 批准号:
    7264425
  • 财政年份:
    2007
  • 资助金额:
    $ 13.62万
  • 项目类别:
eukaryotic expression vectors resistant to transgene silencing
抗转基因沉默的真核表达载体
  • 批准号:
    8256740
  • 财政年份:
    2007
  • 资助金额:
    $ 13.62万
  • 项目类别:
RESEARCH, EDUCATION AND TRAINING
研究、教育和培训
  • 批准号:
    7315454
  • 财政年份:
    2007
  • 资助金额:
    $ 13.62万
  • 项目类别:
eukaryotic expression vectors resistant to transgene silencing
抗转基因沉默的真核表达载体
  • 批准号:
    7264338
  • 财政年份:
    2007
  • 资助金额:
    $ 13.62万
  • 项目类别:
Chimeric enzyme for host nucleic acid autohydrolysis
用于宿主核酸自动水解的嵌合酶
  • 批准号:
    6833053
  • 财政年份:
    2004
  • 资助金额:
    $ 13.62万
  • 项目类别:
Chimeric enzyme for nucleic acid autohydrolysis
用于核酸自水解的嵌合酶
  • 批准号:
    7161099
  • 财政年份:
    2004
  • 资助金额:
    $ 13.62万
  • 项目类别:
Chimeric enzyme for nucleic acid autohydrolysis
用于核酸自水解的嵌合酶
  • 批准号:
    7282957
  • 财政年份:
    2004
  • 资助金额:
    $ 13.62万
  • 项目类别:
MARC U*STAR HONORS UNDERGRAD RESEARCH TRAINING PROGRAM
MARC U*STAR 荣誉本科生研究培训计划
  • 批准号:
    6899155
  • 财政年份:
    1979
  • 资助金额:
    $ 13.62万
  • 项目类别:

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