HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-7303comv1 21/7/1324    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-H. Articles by Lee, J. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-H. Articles by Lee, J.

A novel approach to ultrasensitive diagnosis using supramolecular protein nanoparticles

Sung-Hyun Lee^*,1, Hyewon Lee^*,1, Jin-Seung Park^*, Hyoung Choi^*,2, Kyung-Yeon Han^*, Hyuk-Seong Seo^*, Keum-Young Ahn^*, Sung-Sik Han, Yunjung Cho, Kee-Hyoung Lee and Jeewon Lee^*,3

^* Department of Chemical and Biological Engineering,

School of Life Sciences and Biotechnology,

College of Medicine, Korea University, Seoul 136-713, South Korea

³Correspondence: Department of Chemical and Biological Engineering, Anam-Dong 5-1, Seoul 136-713, South Korea. E-mail: leejw{at}korea.ac.kr

We report on the ultrasensitive protein nanoprobe system that specifically captures disease marker (autoantibodies of Type I diabetes in this case) with attomolar sensitivity. The system relies on supramolecular protein nanoparticles that bind a specific antibody [65 kDa glutamate decarboxylase (GAD₆₅)-specific autoantibody, i.e., the early marker of Type I diabetes]. The ultrasensitive detection of early marker of Type I diabetes during the early phase of pancreatic ß-cell destruction is important because individuals at high risk of developing Type I diabetes can be identified several years before the clinical onset of the ailment. The bacterial expression of chimera genes encoding N-[human ferritin heavy chain (hFTN-H)]::[specific antigenic epitope]-C produces supramolecular nanoparticles with uniform diameters (10–15 nm), owing to self-assembly activity of hFTN-H. Each nanoparticle, formed by intermolecular self-assembly between the chimera protein molecules, is subjected to carrying a large number (presumably, 24) of epitopes with a homogeneous and stable conformation per autoantibody binding, thereby allowing substantial enhancement of sensitivity. The sensitivity was finally boosted to 3 attomolar concentration of the autoantibodies, 4–9 orders of magnitude more sensitive than conventional immunoassays. Also, this ultrasensitive protein nanoprobe successfully detected natural autoantibodies in the sera from Type I diabetic patients. The attomolar sensitivity was successfully reproduced on the detection of other antibodies, i.e., monoclonal antibodies against hepatitis B surface antigen. With the two antibody markers above, the feasibility of simultaneous and multiplexing-mode detection was also demonstrated.—Lee, S-H., Lee, H., Park, J-S., Choi, H., Han, K-Y., Seo, H-S., Ahn, K-Y., Han, S-S., Cho, Y., Lee, K-H., Lee, J. A novel approach to ultrasensitive diagnosis using supramolecular protein nanoparticles.

Key Words: human ferritin heavy chain • nanoprobe system • attomoloar sensitivity