オオサワ　シゲヒト   Oosawa Shigehito   大澤　重仁    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Single-stranded DNA-packaged polyplex micelle as adeno-associated-virus-inspired compact vector to systemically target stroma-rich pancreatic cancer
掲載誌名	正式名：ACS nano. 略　 称：ACS Nano ISSNコード：19360851/1936086X
掲載区分	国外
巻・号・頁	13(11),pp.12732-12742
総ページ数	11
著者・共著者	Theofilus A Tockary, Wanling Foo, Anjaneyulu Dirisala, Qixian Chen, Satoshi Uchida, Shigehito Osawa, Yuki Mochida, Xueying Liu, Hiroaki Kinoh, Horacio Cabral, Kensuke Osada, Kazunori Kataoka
発行年月	2019/10/24
概要	Despite the rigidity of double-stranded DNA (dsDNA), its packaging is used to construct nonviral gene carriers due to its availability and the importance of its double-helix to elicit transcription. However, there is an increasing demand for more compact-sized carriers to facilitate tissue penetration, which may be easily fulfilled by using the more flexible single-stranded DNA (ssDNA) as an alternative template. Inspired by the adeno-associated virus (AAV) as a prime example of a transcriptionally active ssDNA system, we considered a methodology that can capture unpaired ssDNA within the polyplex micelle system (PM), an assembly of DNA and poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLys). A micellar assembly retaining unpaired ssDNA was prepared by unpairing linearized pDNA with heat and performing polyion complexation on site with PEG-PLys. The PM thus formed had a compact and spherical shape, which was distinguishable from the rod-shaped PM formed from dsDNA, and still retained its ability to activate gene expression. Furthermore, we demonstrated that its capacity to encapsulate DNA was much higher than AAV, thereby potentially allowing the delivery of a larger variety of protein-encoding DNA. These features permit the ssDNA-loaded PM to easily penetrate the size-restricting stromal barrier after systemic application. Further, they can elicit gene expression in tumor cell nests of an intractable pancreatic cancer mouse model to achieve antitumor effects through suicide gene therapy. Thus, single-stranded DNA-packaged PM is appealing as a potential gene vector to tackle intractable diseases, particularly those with target delivery issues due to size-restriction barriers.
DOI	10.1021/acsnano.9b04676