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Impact of biophysical and chemical properties of non-viral vector formulation on cell transfection

机译：非病毒载体制剂的生物物理和化学性质对细胞转染的影响

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Many non-viral vectors are limited by unacceptably poor in-vivo cell transfection and low transgene expressions. Experimental evidence suggests that cell transfection efficiency may be linked to particle size, with vector particles below about 200 nm considered desirable. Vector particles are susceptible to aggregation under most conditions of pH and ionic strength including physiological conditions, hence in many cases, particle size exceeds 1000 nm within a few minutes and there are currently no means of predicting the kinetics of aggregation. Recent evidence has demonstrated that vector stability and cell transfection may also be affected by the chemical composition of the vector components. We have developed a lipopolyplex vector consisting of a cationic lipid (L), a peptide with cationic and receptor targeting motifs (I), and plasmid DNA (D). These components assemble electrostatically in solution to form LID vector particles. Here we present data highlighting the impact of composition and physicochemical properties on the stability and cell transfection ability of L:I:D vectors. The lipid component of the initial LID vector used in the study was Lipofectin, (a 1:1 formulation of DOTMA and DOPE), and a peptide component containing a 16 lysine chain molecule. Data is presented from experiments in which the length of the lysine chain was varied systematically in the presence and absence of DOPE.
机译：许多非病毒载体受到不可接受的差的体内细胞转染和低转基因表达的限制。实验证据表明，细胞转染效率可以与粒度连接，载体颗粒低于约200nm认为所需的粒子。在大多数pH和离子强度的大多数条件下，在包括生理条件的大多数条件下，vector颗粒易受聚集，因此在许多情况下，几分钟内粒度超过1000nm，目前没有预测聚集动力学的方法。最近的证据表明，载体稳定性和细胞转染也可能受到载体组分的化学成分的影响。我们开发了一种由阳离子脂质（L），具有阳离子和受体靶向基序（I）的肽（I）的肽和质粒DNA（D）组成的脂多聚合物载体。这些组分在溶液中静电组装以形成盖子载体颗粒。在这里，我们提出了突出了组成和物理化学性质对L：I：D载体的稳定性和细胞转染能力的影响。该研究中使用的初始盖子载体的脂质组分是Lipofectin，（一种单点和涂料的1：1配方），以及含有16个赖氨酸链分子的肽组分。从实验中提出了数据，其中赖氨酸链的长度在存在和不存在涂料中系统地系统地改变。

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