Synthesis and characterization of biodegradable HPMA-oligolysine copolymers for improved gene delivery.
Synthesis and characterization of biodegradable HPMA-oligolysine copolymers for improved gene delivery.
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DOI：
10.1021/bc9003662
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发表时间：
2010-01
影响因子：
4.7
通讯作者：
Pun, Suzie H.
中科院分区：
文献类型：
--
作者：
Burke, Rob S.;Pun, Suzie H.
生物活性肽，包括dna结合肽、内体释放肽和细胞靶向肽，已被整合到合成基因载体中，通过使载体克服基因传递障碍来提高传递效率。我们的总体目标是开发多功能的、基于肽的聚合物，这些聚合物结合基序来浓缩DNA并促进连续的运输步骤。一种方法是通过自由基聚合聚合乙烯基端肽。在这项工作中，阳离子低聚赖氨酸肽被设计成含有乙烯基末端与内部可还原连接。这些肽与HPMA共聚形成可生物降解的dna凝聚共聚物，用于基因传递。通过改变引发剂与单体的比例、大单体与单体的比例和反应物的浓度来优化聚合条件。合成的共聚物被证明具有体内基因传递应用所需的几个重要特性，包括(i)有效的DNA结合和冷凝，（ii）稳定颗粒防止盐诱导聚集的能力，（iii）抵抗细胞外复合体拆封的能力，（iv）生物相容性和细胞摄取后降解为无毒成分的潜力，以及(v)质粒有效地传递到培养细胞。
Bioactive peptides, including DNA-binding, endosomal release and cell targeting peptides, have been integrated into synthetic gene carriers to improve delivery efficiencies by enabling the vectors to overcome barriers to gene delivery. Our overall goal is to develop multifunctional, peptide-based polymers that incorporate motifs to condense DNA and facilitate sequential trafficking steps. One approach is to polymerize vinyl-terminated peptides by radical polymerization. In this work, cationic oligolysine peptides were designed to contain vinyl termini with internal reducible linkers. These peptides were copolymerized with HPMA to form biodegradable, DNA-condensing copolymers for gene delivery. The polymerization conditions were optimized by varying the initiator to monomer ratios, macromonomer to comonomer ratios, and reactant concentrations. The synthesized copolymers were shown to possess several important properties required for in vivo gene delivery applications, including (i) efficient DNA binding and condensation, (ii) the ability to stabilize particles against salt-induced aggregation, (iii) the ability to resist extracellular polyplex unpackaging, (iv) biocompatibility and the potential to be degraded into nontoxic components after cellular uptake, and (v) efficient delivery of plasmid to cultured cells.
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影响因子：
4.7
作者：
Ding, H;Prodinger, WM;Kopecek, J
通讯作者：
Kopecek, J
DOI：
10.1073/pnas.97.2.745
发表时间：
2000-01-18
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Pun, S. H.
影响因子：
4.7
作者：
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通讯作者：
Zhuo, Ren-Xi
影响因子：
4.7
作者：
Gosselin, MA;Guo, WJ;Lee, RJ
通讯作者：
Lee, RJ