2023-09-05 パデュー大学
◆この治療法はマウスモデルで成功し、21日間の研究で治療を受けた腫瘍は増加せず、未治療の腫瘍は3倍に増加しました。治療は特にがん細胞を標的とし、microRNA-34aを用いており、がんの成長を遅らせるだけでなく、がんを促進する遺伝子の活動を抑制します。
◆この治療法は新たながん治療の可能性を示し、既存の薬に耐性のあるがんに対しても効果的である可能性があります。
<関連情報>
- https://www.purdue.edu/newsroom/releases/2023/Q3/first-in-class-targeted-microrna-therapy-slows-cancer-tumor-growth.html
- https://www.nature.com/articles/s41388-023-02801-8
安定性、活性、抗腫瘍効果に優れたファーストインクラスのmiR-34a完全修飾バージョン A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy
Ahmed M. Abdelaal,Ikjot S. Sohal,Shreyas Iyer,Kasireddy Sudarshan,Harish Kothandaraman,Nadia A. Lanman,Philip S. Low & Andrea L. Kasinski
Oncogene Published:05 September 2023
DOI:https://doi.org/10.1038/s41388-023-02801-8
Abstract
Altered by defects in p53, epigenetic silencing, and genomic loss, the microRNA miR-34a represents one of the most clinically relevant tumor-suppressive microRNAs. Without question, a striking number of patients with cancer would benefit from miR-34a replacement, if poor miR-34a stability, non-specific delivery, and delivery-associated toxicity could be overcome. Here, we highlight a fully modified version of miR-34a (FM-miR-34a) that overcomes these hurdles when conjugated to a synthetically simplistic ligand. FM-miR-34a is orders of magnitude more stable than a partially modified version, without compromising its activity, leading to stronger repression of a greater number of miR-34a targets. FM-miR-34a potently inhibited proliferation and invasion, and induced sustained downregulation of endogenous target genes for >120 h following in vivo delivery. In vivo targeting was achieved through conjugating FM-miR-34a to folate (FM-FolamiR-34a), which inhibited tumor growth leading to complete cures in some mice. These results have the ability to revitalize miR-34a as an anti-cancer agent, providing a strong rationale for clinical testing.
