Therapeutic oligonucleotide analogs represent a new and promising family of drugs that act on nucleic acid targets such as RNA or DNA; however, their effectiveness has been limited due to difficulty crossing the cell membrane. A new delivery approach based on cell-penetrating peptide nanoparticles can efficiently transport charge-neutral oligonucleotide analogs into cells, as reported in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Nucleic Acid Therapeutics website.
In the article, "Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides," Peter Järver and coauthors, Cambridge Biomedical Campus (U.K.), Karolinska University Hospital (Huddinge, Sweden), Stockholm University (Sweden), Alexandria University (Egypt), and University of Oxford (U.K.), note that while delivery systems exist to facilitate cell entry of negatively charged oligonucleotide drugs, these approaches are not effective for charge-neutral oligonucleotide analogs. The authors describe lipid-functionalized peptides that form a complex with charge-neutral morpholino oligonucleotides, enabling them to cross into cells and retain their biological activity.
“The exploitation of phosphorodiamidate morpholinos represents an exciting approach to treating a number of therapeutic targets,” says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI. “This paper suggests an intriguing but practical approach to solving the lack of a convenient non-covalent delivery system.”
概要翻译：
治疗性寡核苷酸类似物代表了一种新的有前途的核酸（RNA or DNA）靶向性药物种类。然而，由于很难穿过细胞膜，药物的效用受到限制。一种基于细胞穿透肽纳米颗粒的新的释放方法可以有效地运输的电中性的寡核苷酸类似物进入细胞。
作者说：“电中性的剪接转换反义吗啉代寡核苷酸释放肽纳米颗粒”，并强调出释放系统的存在是为了促使带负电荷的寡核苷酸药物进入细胞，这些方法对电中性的寡核苷酸类似物并不是有效的。
作者描述了脂质修饰的肽形成复合物的电荷中性的吗啉代寡核苷酸，使他们能够进入细胞并保持其生物活性。
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