Heitz Marc, Kwok Albert, Eggimann Gabriela A, Hollfelder Florian, Darbre Tamis, Reymond Jean-Louis
Department of Chemistry and Biochemistry University of Bern Freiestrasse 3, CH-3012 Bern;, Email:
Department of Chemistry and Biochemistry University of Bern Freiestrasse 3, CH-3012 Bern.
Chimia (Aarau). 2017 Apr 26;71(4):220-225. doi: 10.2533/chimia.2017.220.
Transfection reagents are used to deliver DNA and siRNA into cells to achieve genetic manipulations, and may ultimately enable nonviral gene therapy. Progress in transfection reagents is limited by the fact that such reagents cannot be easily optimized due to their polymeric nature and/or difficult synthesis. We have developed a new class of well-defined and easily modifiable transfection reagents in the form of peptide dendrimers. These dendrimers self-assemble with DNA or siRNA and lipofectin to form nanoparticles which efficiently enter mammalian cells and liberate their nucleic acid cargo. By systematically modifying the amino acid sequence of our dendrimers we have found that their transfection efficiency depends on the distribution of positive charges and hydrophobic residues across the dendrimer branches. Positive charges present in all three generations lead to efficient DNA delivery, whereas siRNA delivery requires charges in the outer two generations combined with a hydrophobic dendrimer core.
转染试剂用于将DNA和小干扰RNA（siRNA）导入细胞以实现基因操作，并最终可能实现非病毒基因治疗。转染试剂的进展受到限制，因为此类试剂由于其聚合性质和/或合成困难而不易优化。我们已经开发出一类新型的、定义明确且易于修饰的转染试剂，其形式为肽树枝状大分子。这些树枝状大分子与DNA或siRNA以及脂质转染试剂自组装形成纳米颗粒，这些纳米颗粒能有效地进入哺乳动物细胞并释放其核酸负载。通过系统地修饰我们的树枝状大分子的氨基酸序列，我们发现它们的转染效率取决于树枝状大分子分支上正电荷和疏水残基的分布。所有三代中存在的正电荷导致高效的DNA递送，而siRNA递送则需要外层两代中的电荷与疏水的树枝状大分子核心相结合。
