Antisense activity of 2',4'-BNA targeted to PPAR gamma in THP-1 and HCT116 cells

Tachibana, Keisuke; Katayama, Tatsuya; Ueda, Chihiro; Sumitomo, Mikako; Tagami, Minoru; Ishimoto, Kenji; Yamasaki, Daisuke; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Obika, Satoshi; Imanishi, Takeshi; Doi, Takefumi

doi:10.1093/nass/nrm221

Cited by 1 publication

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“…Treatment of wild-type mice with a PPARγ antagonist has been reported to prevent high fat diet-induced obesity, insulin resistance, and T2D. Tachibana et al designed a third-generation locked nucleic acid targeting the translation initiation site of human PPARγ mRNA and showed its inhibitory effect on two human cell lines (THP-1 and HCT116) (Tachibana et al 2007). PTP-1B negatively regulates insulin receptor in insulinresponsive tissues (such as adipose, liver and muscle).…”

Section: Two Locked Nucleic Acid-modifi Ed Asos For the Cure Of T2dmentioning

confidence: 99%

Nanocarriers of Antisense Oligonucleotides in Diabetes

Rapini

Bottini

Bottini³

2012

Nanotechnology and Nanomedicine in Diabetes

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Antisense oligonucleotides are short strands of deoxyribonucleotides that are complementary to specifi c encoding mRNA sequences and can block gene expression. Their potential use as therapeutic and gene validation tools has elicited great interest. However, poor intracellular delivery into several tissues in living animals currently limits the range of in vivo applications of antisense oligonucleotides. Innovative solutions to this problem are coming from nanomedicine, a discipline recently born from the marriage of nanotechnology and medicine. Through the use of nanotechnology-derived composites (nanocarriers), nanomedicine helps traditional drugs to avoid the body's defenses that the drug encounters following its systemic administration. In this chapter we will describe diabetes-relevant applications of nanocarriers as Nanocarriers of Antisense Oligonucleotides in Diabetes 65delivery systems for antisense oligonucleotides. We divided the chapter in two sections. In the fi rst section we will 1) describe the modes of action of antisense oligonucleotides and the chemical modifi cations that have been developed to ameliorate resistance to nucleases, enhance affi nity and potency, and reduce toxicity; 2) the biological barriers encountered by the antisense oligonucleotides following their systemic administration; 3) the arsenal of solutions that nanomedicine can offer to enable the safe delivery of antisense oligonucleotides to the target site. In the second section, we will review the antisense oligonucleotides and delivery systems that have been developed as novel therapeutic weapons against diabetes. This includes research from our laboratory focusing on achieving targeted delivery of antisense oligonucleotides into T cells for therapy of Type 1 Diabetes.

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Section: Two Locked Nucleic Acid-modifi Ed Asos For the Cure Of T2dmentioning

confidence: 99%