Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen.
Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen.
复制标题
通过炭疽保护性抗原将反义肽核酸寡聚体有效递送至细胞内。
DOI：
10.1016/j.bbrc.2008.08.124
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发表时间：
2008
影响因子：
3.1
通讯作者：
Murphy,JohnR
中科院分区：
文献类型：
--
作者：
Wright,DanielG;Zhang,Ying;Murphy,JohnR
Peptide nucleic acid (PNA) is highly stable and binds to complementary RNA and DNA with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. We investigated whether protectiveantigen (PA, a non-toxic component of anthrax toxin) could transport antisense PNA oligomers into reporter cells that contain luciferase transgenes with mutant β-globin IVS2 intronic inserts, which permit aberrant pre-mRNA splicing and impair luciferase expression. PNA oligomers antisense to mutant splice sites in these IVS2 inserts induced luciferase expression when effectively delivered into the cells. PNA 18-mers with C-terminal poly-lysine tails [PNA(Lys)8] demonstrated modest sequence-specific antisense activity by themselves at micromolar concentrations in luc-IVS2 reporter cell cultures. However, this activity was greatly amplified by PA. Antisense PNA(Lys)8with but not without PA also corrected the IVS2-654 β-globin splice defect in cultured erythroid precursor cells from a patient with β-thalassemia [genotype, IVS2-654(β0/βE)], providing further evidence that anthrax PA can effectively transport antisense PNA oligomers into cells.
