Search

CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. [ABSTRACT FROM AUTHOR]

CRISPR Gene TherapyIn article number 2308095, Wei Li, Fei Teng, and colleagues introduce a hypercompact CRISPR‐Cas12f1 system characterized by enhanced gene editing capabilities and minimal off‐target effects. Applied to the treatment of inherited retinal diseases, this system shows significant therapeutic outcomes, highlighting its substantial promise for gene therapy applications..By Tongtong Cui; Bingyu Cai; Yao Tian; Xin Liu; Chen Liang; Qingqin Gao; Bojin Li; Yali Ding; Rongqi Li; Qi Zhou; Wei Li and Fei TengReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

The increasing interest in environmental conservation is a global phenomenon. In many countries, natural reserves or protected areas (PAs) have been established to restrict human activities and to enhance natural ecosystems, which potentially benefit the planet as a whole. However, this often demands some sacrifices from local residents who may have to give up resources they rely on or suffer losses caused by wildlife. This issue potentially becomes aggravated in densely populated areas where many people and economic activities are impacted. This paper presents research findings on poverty issues in a newly established national natural reserve in China, Hengshui Lake Natural Reserve. The paper addresses the characteristics of poor households in the reserve and the interaction between these families and the reserve. In addition, poverty alleviation measures are analysed and additional measures to reduce poverty and conflicts between the reserve and local residents are recommended. [ABSTRACT FROM AUTHOR]