JP2022543446A - Apoe4 rna特異的トランススプライシングリボザイム及びその用途 - Google Patents
Apoe4 rna特異的トランススプライシングリボザイム及びその用途 Download PDFInfo
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Abstract
Description
Claims (17)
- APOE4 RNA序列を標的とする、トランススプライシングリボザイム。
- 前記トランススプライシングリボザイムは、5’-IGS-リボザイム*-エクソン-3’の構造を有することを特徴とする、請求項1に記載のトランススプライシングリボザイム。
- 前記IGS領域は、APOE4 RNAの+21、+30、+49、+56、+71、+77、+80、+82、+95、+98、+104、+128、+140、+181、+229、+255、+263、+275、+326、+368、+830、又は+839塩基を含む領域と相補的に結合される5~10ntの長さの塩基配列からなることを特徴とする、請求項2に記載のトランススプライシングリボザイム。
- 前記IGS領域は、序列番号2、4、又は6の塩基配列を含むことを特徴とする、請求項3に記載のトランススプライシングリボザイム。
- 前記トランススプライシングリボザイムは、IGS領域のアップストリームにAPOE4 RNAの一部と相補的に結合される10nt~200ntの長さのAS領域をさらに含むことを特徴とする、請求項2に記載のトランススプライシングリボザイム。
- 前記IGS領域は序列番号2の塩基配列を含み、前記AS領域は150ntの長さであることを特徴とする、請求項5に記載のトランススプライシングリボザイム。
- 前記IGS領域は序列番号4の塩基配列を含み、前記AS領域は50ntの長さであることを特徴とする、請求項5に記載のトランススプライシングリボザイム。
- 前記IGS領域及びAS領域は、5~10ntの長さのランダム塩基配列に連結されていることを特徴とする、請求項5に記載のトランススプライシングリボザイム。
- 前記リボザイム*領域は、序列番号5の塩基配列を含むことを特徴とする、請求項2に記載のトランススプライシングリボザイム。
- 前記エクソン領域は、ApoE2又はApoE3クライストチャーチ突然変異(R136S)を暗号化する塩基配列の一部又は全てを含むことを特徴とする、請求項2に記載のトランススプライシングリボザイム。
- 請求項1~10のいずれか一項に記載のトランススプライシングリボザイムを発現できる、発現ベクター。
- 前記発現ベクターは、前記リボザイム遺伝子と作動可能に連結されたプロモータをさらに含むことを特徴とする、請求項11に記載の発現ベクター。
- 前記プロモータは、神経細胞タイプの特異的なプロモータであることを特徴とする、請求項12に記載の発現ベクター。
- 前記神経細胞タイプの特異的なプロモータは、ニューロン-、星状細胞-又は希突起膠細胞-特異的プロモータであることを特徴とする、請求項13に記載の発現ベクター。
- 請求項1~10に記載のトランススプライシングリボザイム、請求項11~14に記載の発現ベクター、及び前記発現ベクターを含む遺伝子伝達システムからなる群から選択されるいずれか1つを有効成分として含むアルツハイマー病の予防又は治療用医薬組成物。
- 請求項1に記載のトランススプライシングリボザイム、これを発現できるベクター、及び前記ベクターを含む遺伝子伝達システムからなる群から選択されるいずれか1つ以上を個体に投与することを含む、アルツハイマー病の予防又は治療方法。
- アルツハイマー病の予防又は治療薬剤の製造のための請求項1に記載のトランススプライシングリボザイム、これを発現できるベクター、又は前記ベクターを含む遺伝子伝達システムの用途。
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KR10-2021-0025822 | 2021-02-25 | ||
PCT/KR2021/002443 WO2021172925A1 (ko) | 2020-02-28 | 2021-02-26 | Apoe4 rna 특이적 트랜스-스플라이싱 리보자임 및 이의 용도 |
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