JP2018531004A - 光受容器のターゲッティングにより失明を治療するための新規な治療用ツールおよび方法 - Google Patents
光受容器のターゲッティングにより失明を治療するための新規な治療用ツールおよび方法 Download PDFInfo
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Abstract
Description
本発明は、失明の治療方法に関する。本発明はまた、失明を治療する際に使用するための構築物、ならびに失明治療用の医薬の製造におけるそれらの使用に関する。
失明は、世界中の何百万人もの人々に障害を与える大きな健康問題である。最も多い失明原因の一つに、網膜の機能不全がある。網膜性の失明で最も多いのが、網膜色素変性症(RP)、黄斑変性(MD)および緑内障(G)の3タイプである。RPおよびMDにおける主要な問題は、光受容器の変性およびそれに伴う光感受性の喪失である。ゆえに、かかる光受容器の変性に伴う問題の解消を可能にすることに対するニーズが存在する。
更なる研究において、本発明者らは、網膜光受容器における脱分極性光感受性分子の発現が、例えば視力回復に非常に有用であり得ることを知るに至った。網膜光受容器を活性化させるには、通常では過分極が必要であるため、そこで脱分極性光感受性分子を発現させることは常識に反することであるが、本発明者らは、この発現が驚く程有用であり、驚くほど良好に機能するのみならず、例えば、それぞれの網膜細胞内での外生的な感光性分子の発現を用いた視力回復方法において、全体的な網膜応答の調節をも可能にすることを見出した。本発明者は更に、疾患状態においては、網膜光受容器の分極が通常の状態を必ずしも反映せず、健常な網膜光受容器と比較し、場合によっては逆になることさえあり得ることをも見出した。
更なる研究において、本発明者らは、網膜光受容器における脱分極性光感受性分子の発現が、例えば視力回復に非常に有用であり得ることを知るに至った。網膜光受容器を活性化させるには、通常では過分極が必要であるため、そこで脱分極性光感受性分子を発現させることは常識に反することであるが、本発明者らは、この発現が驚く程有用であり、驚くほど良好に機能するのみならず、例えば、それぞれの網膜細胞内での外生的な感光性分子の発現を用いた視力復元方法において、全体的な網膜応答の調節をも可能にすることを見出した。本発明者は更に、疾患状態においては、網膜光受容器の分極が通常の状態を必ずしも反映せず、健常な網膜光受容器と比較し、場合によっては逆になることさえあり得ることをも見出した。
Fabp7(trunc)(配列番号1)
Claims (10)
- 網膜光受容器において脱分極性光駆動性イオンチャネルの特異的な発現をもたらすプロモーターに機能的に連結された、前記脱分極性光駆動性イオンチャネルをコードするヌクレオチド配列または前記ヌクレオチド配列と相補的なヌクレオチド配列を含む、失明の治療または改善に用いられる、単離された核酸分子。
- 前記脱分極性光駆動性イオンチャネルが、チャネルロドプシン、例えばチャネルロドプシン−2またはその変異体である、請求項1に記載の単離された核酸分子。
- 網膜光受容器で前記脱分極性光駆動性イオンチャネルの発現をもたらす前記プロモーターが、ヒトロドプシンプロモーター、ヒト赤オプシンプロモーター、赤錐体オプシンプロモーター、arr3プロモーター(mCAR)、Grm6プロモーター、Fabp7(trunc)(配列番号1)、Gnat2_500(配列番号2)、Gnat2_2kb(配列番号3)、Arr3_2kb(配列番号4)、TF_ZFHX3(配列番号5)およびTF_GSH2(配列番号6)の群から選択される、請求項1または2に記載の単離された核酸分子。
- 前記網膜光受容器細胞が、桿体細胞および/または錐体細胞である、請求項1から3のいずれか1項に記載の単離された核酸分子。
- 配列番号1、2、3、4、5または6の核酸配列を含むか、もしくはそれからなるか、または、前記配列番号1、2、3、4、5または6のそれぞれの配列と少なくとも90%の相同性を有する、少なくとも200bpの核酸配列からなる単離された核酸分子であって、網膜光受容器の遺伝子をコードする核酸配列が、前記単離された核酸分子に作動可能に連結されたとき、前記遺伝子の発現を特異的にもたらす、前記単離された核酸分子。
- 請求項1から5のいずれか1項に記載の核酸を含む組換えベクター。
- 請求項6に記載のベクターを含む宿主細胞。
- 請求項1から5のいずれか1項に記載の単離された核酸、請求項6に記載の組換えベクター、または請求項7に記載の宿主細胞を含むキット。
- 請求項1から5のいずれか1項に記載の単離された核酸、請求項6に記載の組換えベクター、または請求項7に記載の細胞を、失明の治療を必要とする患者に投与することを特徴とする、失明の治療方法
- 前記投与が、網膜下注射を通じて行われる、請求項9に記載の失明の治療方法。
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