マイクロRNAによる遺伝子発現制御システムを搭載した 遺伝子組換えアデノウイルスの開発
スポンサーリンク
概要
- 論文の詳細を見る
Target tissue-specific delivery and transcription of foreign genes are desirable for safe and effective gene therapy. Two approaches for this purpose, “Targeted Delivery” and “Targeted Expression”, have been mainly reported. Among “Targeted Expression” approaches, microRNA (miRNA)-mediated “post-transcriptional de-targeting” has been recently demonstrated, and much attention has been focused on this approach. MiRNAs are an approximately 22-nt length non-coding RNA, and bind to imperfectly complementary sequences in the 3′-untranslated region (UTR) of target mRNA, leading to suppression of gene expression via post-transcriptional regulation. First, in order to reduce the hepatic transduction by Ad vectors, complementary sequences of liver-specific miRNA, miR-122a, were inserted into the 3′-UTR of the transgene expression cassette. Intratumor injection of this Ad vector resulted in approximately 100-fold lower hepatic expression than that of the conventional Ad vector, without reducing gene expression in the tumor. Second, complementary sequences for miRNAs selectively down-regulated in tumor cells were inserted into the E1 gene expression cassette in oncolytic Ads, which exhibit tumor cell-specific replication and antitumor effects. Recent studies demonstrated that expression of several miRNAs is exclusively reduced in tumor cells. Oncolytic Ads containing the miRNA complementary sequences showed reduced replication in the normal cells, without altering the antitumor effects. MiRNA-regulated gene expression system mediates “post-transcriptional de-targeting”, in which translation of transgene is suppressed in a tissue-specific manner; however, tissue-specific transgene expression can be achieved by taking tropism of gene delivery vehicles into consideration and reducing the transgene expression in untargeted organs via miRNA-regulated gene expression system.
著者
関連論文
- OP-039 膀胱癌細胞株に対するアデノウイルスベクターの導入効率向上の試み(尿路上皮/基礎,一般演題口演,第97回日本泌尿器科学会総会)
- 標的指向能を有するバイオコンジュゲート化アデノウイルスベクターの開発(誌上シンポジウム)
- 次世代アデノウイルスベクターの開発と生命科学研究への応用 : 第10回日本DDS学会永井賞受賞によせて
- 組換えウイルスキャリア-遺伝子治療・ワクチン応用への新展開- : 特集によせて
- iPS細胞への遺伝子導入を用いた分化誘導の最適化
- マイクロRNAによる遺伝子発現制御システムを搭載した 遺伝子組換えアデノウイルスの開発
- 生理活性タンパク質による治療最適化を指向した遺伝子・細胞製剤の開発
- Development of a Novel Adenovirus Vector Exhibiting MicroRNA-mediated Suppression of the Leaky Expression of Adenovirus Genes
- Development of a Detection System for Circulating Tumor Cells in Peripheral Blood Using a Next Generation Conditionally-replicating Adenovirus
- Development of an Adenovirus Vector Containing a Hepatitis C Virus Expression Cassette and Its Application
- New Approaches to Drug Discovery Research and Medical Treatment Using Viruses—Viruses Are Valuable Biomaterials—