Design of Free Triblock Polylysine-b-Polyleucine-b-Polylysine Chains for Gene Delivery,Biomacromolecules

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Design of Free Triblock Polylysine-b-Polyleucine-b-Polylysine Chains for Gene Delivery
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1021/acs.biomac.8b00287
Baizhu Chen ₁ , Lei Yu ₂ , Zhibo Li ₂ , Chi Wu _{1,

3}

Affiliation

Mixing cationic polymer chains with anionic DNA chains in solution results in the polymer/DNA complexes (also known as polyplexes). We recently confirmed that it is those noncomplexed cationic chains free in the mixture that promote the gene transfection, leading to a hypothesis: free cationic chains adsorbed on various anionic membranes interfere with the signal protein interaction, disrupt the intervesicular fusion, and block the endolysosome pathway so that the plasmid DNA (pDNA) chains have a higher chance to enter the nucleus. Accordingly, we design and synthesize linear cationic–hydrophobic–cationic triblock polylysine (K)-b-polyleucine (L)-b-polylysine (K) as free cationic chains by using natural protamine to condense the pDNA. The hydrophobic middle L-block helps its insertion into the membrane, while the interaction of the two cationic side K-blocks with the signal proteins helps the escape of the polyplexes from the lysosome entrapment. We studied the transfection efficiency of these copolymers with different block lengths. We found the optimal length of blocks K and L that allows the free triblock cationic copolymer chains to effectively enhance the gene transfection process. A combination of copolypeptides and protamine provides a new kind of biocompatible and nontoxic gene vectors made of only nontoxic peptides.

中文翻译：

免费三嵌段聚赖氨酸的设计b -Polyleucine- b基因传递链条ε-聚赖氨酸

在溶液中将阳离子聚合物链与阴离子DNA链混合会形成聚合物/ DNA复合物（也称为多复合物）。我们最近证实，混合物中游离的那些非复杂阳离子链可促进基因转染，从而得出一个假设：吸附在各种阴离子膜上的游离阳离子链会干扰信号蛋白相互作用，破坏囊泡融合并阻断溶酶体途径因此质粒DNA（pDNA）链有更高的机会进入细胞核。因此，我们设计并合成线性阳离子疏水阳离子三嵌段聚赖氨酸（K） - b -polyleucine（L） - b-聚赖氨酸（K）作为游离阳离子链，通过使用天然鱼精蛋白浓缩pDNA。疏水性中间L-嵌段有助于其插入膜中，而两个阳离子侧K-嵌段与信号蛋白的相互作用则有助于多聚体从溶酶体的捕获中逸出。我们研究了不同嵌段长度的这些共聚物的转染效率。我们发现了允许自由的三嵌段阳离子共聚物链有效地增强基因转染过程的嵌段K和L的最佳长度。共多肽和鱼精蛋白的组合提供了一种仅由无毒肽组成的新型生物相容性和无毒基因载体。

更新日期：2018-03-05

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