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- W133044283 abstract "Antisense oligonucleotides (ASO) against specific molecular targets (e.g., Bcl-2 and Raf-1) are important reagents in cancer biology and therapy. Phosphorothioate modification of the ASO backbone has resulted in an increased stability of ASO in vivo without compromising, in general, their target selectivity. Although the power of antisense technology remains unsurpassed, dose-limiting side effects of modified ASO and inadequate penetration into the tumor tissue have necessitated further improvements in ASO chemistry and delivery systems. Oligonucleotide delivery systems may increase stability of the unmodified or minimally modified ASO in plasma, enhance uptake of ASO by tumor tissue, and offer an improved therapy response. Here, we provide an overview of ASO design and in vivo delivery systems, and focus on preclinical validation of a liposomal nanoparticle containing minimally modified raf antisense oligodeoxynucleotide (LErafAON). Intact rafAON (15-mer) is present in plasma and in normal and tumor tissues of athymic mice systemically treated with LErafAON. Raf-1 expression is decreased in normal and tumor tissues of LErafAON-treated mice. Therapeutic benefit of a combination of LErafAON and radiation or an anticancer drug exceeds radiation or drug alone against human prostate, breast, and pancreatic tumors grown in athymic mice. Further improvements in ASO chemistry and nanoparticles are promising avenues in antisense therapy of cancer." @default.
- W133044283 created "2016-06-24" @default.
- W133044283 creator A5004545491 @default.
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- W133044283 creator A5072559983 @default.
- W133044283 creator A5080775024 @default.
- W133044283 date "2006-12-16" @default.
- W133044283 modified "2023-09-24" @default.
- W133044283 title "Antisense Oligonucleotides: Target Validation and Development of Systemically Delivered Therapeutic Nanoparticles" @default.
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- W133044283 doi "https://doi.org/10.1385/1-59745-208-4:163" @default.
- W133044283 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17172711" @default.
- W133044283 hasPublicationYear "2006" @default.
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