Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
基本信息
- 批准号:RGPIN-2016-04009
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The most commonly applied method for facilitating the transfer of DNA into cells is through the use of viral vectors, which are the most efficient vectors currently being studied, accounting for more than 65% of ongoing clinical trials. Viral vectors have several potential disadvantages for application as a gene therapy; most significantly, very real safety concerns exist because viral capsids have the potential to generate a severe immune response, cause mutagenisis , as has been demonstrated in a number of animal experiments and human trials, where patient death (resulting from adenoviral vector) has been reported. An alternative approach is to use self-assembling nanoparticles that are capable of binding DNA and delivering it into the cells. These non-viral systems are typically based upon positively charged lipids or polymers, and are generally non-immunogenic and have low toxicities; however, they also suffer from low efficiency in terms of DNA delivery.
Our work is focused on the design of new non-viral delivery systems based upon neutral polymers that are non-toxic, are easily cleared from the body, and are biodegradable in the environment. This proposal focuses on the application of naturally occurring polymers, in this case gelatin, to the formation of nanoparticle vectors for the delivery of DNA. Naturally occurring gelatin will be converted to a cationic form, allowing for efficient packaging of DNA. The gelatin/DNA complexes will then be formulated with other components to enhance the overall expression of the protein of interest, in this case the enhanced green fluorescent protein which is used as a reporter gene for analysis purposes. In particular, we will explore the impact of the cationic gelatin nanoparticles on lipid membranes, utilizing lipid monolayers as a model of cellular membranes implicated in transfection (i.e. plasma membrane, endosomal membrane, etc.). The structure of model membranes will be examined using Langmuir isotherm methods coupled with Brewster Angle Microscopy (BAM), Infra-red reflected absorbance spectroscopy (IRRAS) and Atomic Force Microscopy (AFM). From these studies we hope to determine relationships between nanoparticle composition and the impact on membrane structure, allowing for better prediction of which nanoparticle formulations are more likely to be successful as DNA transfection vectors.
促进DNA转移到细胞中最常用的方法是使用病毒载体,这是目前正在研究的最有效的载体,占正在进行的临床试验的65%以上。病毒载体作为基因治疗有几个潜在的缺点;最重要的是,存在非常现实的安全问题,因为病毒衣壳有可能产生严重的免疫反应,导致诱变,正如在许多动物实验和人体试验中所证明的那样,已经报告了患者死亡(由腺病毒载体引起)。另一种方法是使用能够结合DNA并将其传递到细胞中的自组装纳米颗粒。这些非病毒系统通常基于带正电的脂质或聚合物,通常是非免疫原性的,毒性低;然而,它们在DNA传递方面也存在效率低下的问题。
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)
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Wettig, Shawn其他文献
Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
- DOI:
10.3390/pharmaceutics11040179 - 发表时间:
2019-04-01 - 期刊:
- 影响因子:5.4
- 作者:
Aborig, Mohamed;Malik, Paul R. V.;Wettig, Shawn - 通讯作者:
Wettig, Shawn
Synthesis of curcumin-functionalized gold nanoparticles and cytotoxicity studies in human prostate cancer cell line
- DOI:
10.1007/s13204-018-0728-6 - 发表时间:
2018-03-01 - 期刊:
- 影响因子:0
- 作者:
Nambiar, Shruti;Osei, Ernest;Wettig, Shawn - 通讯作者:
Wettig, Shawn
Topical non-invasive gene delivery using gemini nanoparticles in interferon-γ-deficient mice
- DOI:
10.1016/j.ejpb.2007.01.002 - 发表时间:
2007-03-01 - 期刊:
- 影响因子:4.9
- 作者:
Badea, Ildiko;Wettig, Shawn;Foldvari, Marianna - 通讯作者:
Foldvari, Marianna
Fluorescence-based techniques to assess the miscibility and physical stability of a drug-lipid complex
- DOI:
10.1139/cjc-2018-0404 - 发表时间:
2019-06-01 - 期刊:
- 影响因子:1.1
- 作者:
Huang, Jiahao;Chen, Peter X.;Wettig, Shawn - 通讯作者:
Wettig, Shawn
Wettig, Shawn的其他文献
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{{ truncateString('Wettig, Shawn', 18)}}的其他基金
Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
- 批准号:
RGPIN-2016-04009 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
- 批准号:
RGPIN-2016-04009 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
- 批准号:
RGPIN-2016-04009 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
- 批准号:
RGPIN-2016-04009 - 财政年份:2017
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Gelatin-based nanoparticles as DNA transfection vectors
明胶纳米颗粒作为 DNA 转染载体
- 批准号:
RGPIN-2016-04009 - 财政年份:2016
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Pluronic-based nanoparticles as novel DNA transfection vectors
基于 Pluronic 的纳米粒子作为新型 DNA 转染载体
- 批准号:
355626-2011 - 财政年份:2015
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Pluronic-based nanoparticles as novel DNA transfection vectors
基于 Pluronic 的纳米粒子作为新型 DNA 转染载体
- 批准号:
355626-2011 - 财政年份:2014
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Pluronic-based nanoparticles as novel DNA transfection vectors
基于 Pluronic 的纳米粒子作为新型 DNA 转染载体
- 批准号:
355626-2011 - 财政年份:2013
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Pluronic-based nanoparticles as novel DNA transfection vectors
基于 Pluronic 的纳米粒子作为新型 DNA 转染载体
- 批准号:
355626-2011 - 财政年份:2012
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Pluronic-based nanoparticles as novel DNA transfection vectors
基于 Pluronic 的纳米粒子作为新型 DNA 转染载体
- 批准号:
355626-2011 - 财政年份:2011
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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