Core Viewpoint - The article discusses the development of a compact and efficient CRISPR activation platform, HEAL, based on dCas12f, which enhances gene activation capabilities and is suitable for in vivo applications, addressing limitations of traditional CRISPR systems [4][15]. Group 1: HEAL System Development - The HEAL platform is designed to be smaller, more powerful, and flexible in its regulatory approach, achieving up to 100,000-fold transcriptional activation of endogenous genes [4][5]. - The system utilizes a compact dCas12f protein and is compatible with AAV delivery, overcoming the size limitations of traditional CRISPR systems [7][15]. - Structural optimization of sgRNA and engineering of dCas12f significantly improved the system's transcriptional activation strength [8]. Group 2: Applications and Innovations - The HEAL system allows for precise temporal and spatial control of gene activation through a light-inducible system (OptoHEAL) and a small molecule-inducible system (ChemHEAL) [10][15]. - In vivo experiments demonstrated that the HEAL system could effectively activate the Il10 gene in mice, alleviating acute kidney injury symptoms [11][13]. - The ChemHEAL system was shown to control Tslp expression in obese mice, leading to a significant reduction in body weight [12][14]. Group 3: Implications for Future Research - The HEAL platform represents a significant advancement in gene therapy, providing a powerful tool for gene function studies, disease modeling, and potential therapeutic applications [15].