Flynn S M, George S T, White L, Devonish W, Takle G B
Innovir Laboratories, Wilmington, DE, USA.
Biotechniques. 1999 Apr;26(4):736-42, 744, 746. doi: 10.2144/99264rr03.
The delivery of oligonucleotides to appropriate intracellular compartments is crucial to their development as tools in gene function studies and as therapeutics. Here, we report the characterization of meso-substituted cationic porphyrins as a large class of water-soluble reagents for oligonucleotide delivery. These porphyrins form non-covalent complexes with single-stranded oligonucleotides and deliver these molecules into the nuclei of cell lines in culture. The porphyrins protect oligonucleotides from nuclease degradation, and delivery is unaffected by the presence of serum. Delivery capacity is dependent on the charge ratio and concentration of the oligonucleotide and porphyrin used to form the complex, on the chemical substituents of the oligonucleotide and on the identity of the cationic porphyrin. This class of molecules provides a versatile set of water-soluble delivery reagents that could contribute to the development of oligonucleotide drugs.
将寡核苷酸递送至合适的细胞内区室对于其作为基因功能研究工具和治疗剂的开发至关重要。在此,我们报道了中位取代的阳离子卟啉作为一大类用于寡核苷酸递送的水溶性试剂的特性。这些卟啉与单链寡核苷酸形成非共价复合物,并将这些分子递送至培养的细胞系细胞核中。卟啉可保护寡核苷酸免受核酸酶降解,且血清的存在不影响递送。递送能力取决于用于形成复合物的寡核苷酸和卟啉的电荷比及浓度、寡核苷酸的化学取代基以及阳离子卟啉的特性。这类分子提供了一组通用的水溶性递送试剂,可有助于寡核苷酸药物的开发。
Org Lett. 2005-12-8
J Am Soc Mass Spectrom. 2012-6-12
J Am Soc Mass Spectrom. 2012-4-12