A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3′ or 5′ end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.
一种增强抗菌活性的反义寡核苷酸方法,其由
磷含量的亚单位连接的morpholino亚单位组成,至少增强了10倍的抗菌活性。该方法包括以下一项或两项:将富含精
氨酸的载体与寡核苷酸的3'或5'端结合,并修改寡核苷酸,使其在生理pH下含有20%-50%的亚单位连接具有正电荷。此外,还披露了一种由于一项或两项修改而具有增强抗菌活性的反义寡核苷酸。