کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10613494 | 986890 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Optimization of nuclear localization signal for nuclear transport of DNA-encapsulating particles
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی مواد
بیومتریال
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The nuclear membrane is a tight barrier against the delivery of therapeutic genes into non-dividing tissue cells. Overcoming this barrier with the aid of peptidic nuclear localization signals (NLS) is crucial for improving the performance of synthetic gene-delivery vehicles. In this article, we examine the nuclear transport of lambda phage particles displaying various peptides containing the minimum NLS of SV40 T antigen on their surface. As the minimum NLS (PKKKRKV) is a binding domain to importin α, recombinant proteins and molecular conjugates containing this peptide accumulate into the nucleus efficiently. However, we find that the C-terminal and N-terminal structures besides the minimum NLS profoundly affect the efficiency of the nuclear transport of the phage particles as well as their binding capacity to importin α: either truncation of a few amino acid residues from the C-terminus or the replacement of the N-terminus with a FLAG- or c-myc-tag abolish both of these biological activities. The structure of the optimized NLS is unpredictable from conventional protein transport assay and from the structural analysis in silico. Our results reveal that the objects with 50 nm in diameter can pass through the nuclear pore complex when the optimized NLS is displayed at a sufficient density on their surface.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 104, Issue 3, 2 June 2005, Pages 507-519
Journal: Journal of Controlled Release - Volume 104, Issue 3, 2 June 2005, Pages 507-519
نویسندگان
Akiko Eguchi, Hiroyuki Furusawa, Akitsugu Yamamoto, Teruo Akuta, Mamoru Hasegawa, Yoshio Okahata, Mahito Nakanishi,