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首页> 外文期刊>Biomaterials Science >A triple chain polycationic peptide-mimicking amphiphile - efficient DNA-transfer without co-lipids
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A triple chain polycationic peptide-mimicking amphiphile - efficient DNA-transfer without co-lipids

机译：三链聚合肽 - 模仿两亲的 - 有效的DNA转移而无需共脂质

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摘要

Non-viral gene delivery in its current form is largely dependent upon the ability of a delivery vehicle to protect its cargo in the extracellular environment and release it efficiently inside the target cell. Also a simple delivery system is required to simplify a GMP conform production if a marketing authorization is striven for. This work addresses these problems. We have developed a synthetic polycationic peptide-mimicking amphiphile, namely DiTT4, which shows efficient transfection rates and good biocompatibility without the use of a co-lipid in the formulation. The lipid-nucleic acid complex (lipoplex) was characterized at the structural (electron microscopy), physical (laser Doppler velocimetry and atomic force microscopy) and molecular levels (X-ray scattering). Stability studies of the lipoplexes in the presence of serum and heparin indicated a stable formation capable of protecting the cargo against the extracellular milieu. Hemocompatibility studies (hemolysis, complement activation and erythrocyte aggregation) demonstrated the biocompatibility of the formulation for systemic administration. The transfection efficiency was assessed in vitro using the GFP assay and confocal laser scanning microscopy studies. With the chorioallantoic membrane model, an animal replacement model according to the 3R strategy (replacement, refinement, and reduction), initial in vivo experiments were performed which demonstrate fast and efficient transfection in complex tissues and excellent biocompatibility.
机译：其目前形式的非病毒基因递送在很大程度上取决于递送载体在细胞外环境中保护其货物的能力并有效地在靶细胞内释放。还需要一个简单的交付系统，以简化GMP，如果营销授权是争取的。这项工作解决了这些问题。我们开发了一种合成的聚阳离子肽 - 模仿两亲，即DITT4，其显示出有效的转染率和良好的生物相容性，而不使用制剂中的共脂质。脂质核酸复合物（Lipoplex）在结构（电子显微镜），物理（激光多普勒速度和原子力显微镜）和分子水平（X射线散射）处。血清和肝素存在下脂肪量的稳定性研究表明了能够保护货物免受细胞外环境的稳定性形成。血液相位性研究（溶血，补体和红细胞聚集）证明了系统施用制剂的生物相容性。使用GFP测定和共聚焦激光扫描显微镜研究在体外进行转染效率。利用斗脉膜模型，进行了根据3R策略（更换，细化和减少）的动物替代模型，进行了初始体内实验中的初始实验，其在复杂组织中表现出快速有效的转染和优异的生物相容性。

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  • 来源
    《Biomaterials Science》 |2020年第1期|共18页
  • 作者

    Pinnapireddy Shashank Reddy; Giselbrecht Julia; Strehlow Boris; Janich Christopher; Husteden Catharina; Meister Annette; Loppnow Harald; Sedding Daniel; Erdmann Frank; Hause Gerd; Brezesinski Gerald; Groth Thomas; Langner Andreas; Bakowsky Udo; Woelk Christian;

  • 作者单位

    Univ Marburg Dept Pharmaceut &

    Biopharmaceut Robert Koch Str 4 D-35037 Marburg Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Med Chem Wolfgang Langenbeck Str 4 D-06120 Halle Saale Germany;

    Univ Marburg Dept Pharmaceut &

    Biopharmaceut Robert Koch Str 4 D-35037 Marburg Germany;

    Univ Marburg Dept Pharmaceut &

    Biopharmaceut Robert Koch Str 4 D-35037 Marburg Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Med Chem Wolfgang Langenbeck Str 4 D-06120 Halle Saale Germany;

    Martin Luther Univ Halle Wittenberg Inst Biochem &

    Biotechnol Kurt Mothes Str 3a D-06120 Halle Germany;

    Martin Luther Univ Halle Wittenberg Fac Med Internal Med 3 Ernst Grube Str 40 D-06120 Halle Saale Germany;

    Martin Luther Univ Halle Wittenberg Fac Med Internal Med 3 Ernst Grube Str 40 D-06120 Halle Saale Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Pharmacol Wolfgang Langenbeck Str 4 D-06120 Halle Saale Germany;

    Martin Luther Univ Halle Wittenberg Bioctr Weinbergweg 22 D-06120 Halle Germany;

    Max Planck Inst Colloids &

    Interfaces Sci Pk Potsdam Golm Muhlenberg 1 D-14476 Potsdam Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Biomed Mat Heinrich Damerow Str 4 D-06120 Halle Saale Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Med Chem Wolfgang Langenbeck Str 4 D-06120 Halle Saale Germany;

    Univ Marburg Dept Pharmaceut &

    Biopharmaceut Robert Koch Str 4 D-35037 Marburg Germany;

    Martin Luther Univ Halle Wittenberg Inst Pharm Dept Med Chem Wolfgang Langenbeck Str 4 D-06120 Halle Saale Germany;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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