کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1427637 1509088 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endosome trapping limits the efficiency of splicing correction by PNA-oligolysine conjugates
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Endosome trapping limits the efficiency of splicing correction by PNA-oligolysine conjugates
چکیده انگلیسی

Splicing correction by steric-blocking oligonucleotides (ON) might lead to important clinical applications but requires efficient delivery to cell nuclei. The conjugation of short oligolysine tails has been used to deliver a correcting peptide nucleic acid (PNA) sequence in a positive readout assay in which ON hybridization to the cryptic splice site is strictly required for the expression of a luciferase reporter gene. We have investigated the mechanism of cellular uptake and the efficiency of a (Lys)8-PNA-Lys construction in this model system. Cell uptake is temperature-dependent and leads to sequestration of the conjugate in cytoplasmic vesicles in keeping with an endocytic mechanism of internalization. Accordingly a significant and sequence-specific splicing correction is achieved only in the presence of endosome-disrupting agents as chloroquine or 0.5 M sucrose. These endosome-disrupting agents do not affect the activity of free PNA, and do not increase (Lys)8-PNA-Lys uptake.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 110, Issue 3, 21 February 2006, Pages 595–604
نویسندگان
, , , , , ,