Since the identification of DNA as a genetic material, manipulating DNA in various organisms has been a long standing dream of humanity. In pursuit of this objective, technologies to edit genome have been extensively developed over the recent decades. The emergence of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems enabled site-specific DNA cleavage in a programmable manner. Furthermore, the advent of base editors (BEs) and prime editors (PEs) has enabled base conversion and insertion/deletion with a high accuracy. In addition to the editing of genomic DNA in the nucleus, attempts to manipulate circular DNAs in organelle are currently ongoing. These technologies are bringing major progress in diverse fields including the engineering of cells, livestock, and plants as well as therapeutic gene correction in humans. In this special issue, we aim to cover the recent advances in genome editing technology and its applications in therapeutics, breed improvement in plants and livestock, RNA recording, and protein evolution. [BMB Reports 2024; 57(1): 1].

In this issue of Molecular Cell, Bao et al.1 set out to elucidate \"functional lysines\" in the genome using adenine base editors. The study reveals several cases of alteration of functions that previous canonical CRISPR-Cas9 screens were unable to detect.

The advent of genome editing platforms such as the CRISPR/Cas9 system ushers an unprecedented speed in the development of new crop varieties that can withstand the agricultural challenges of the 21st century. The CRISPR/Cas9 system depends on the specificity of engineered single guide RNAs (sgRNAs). However, sgRNA design in plants can be challenging due to the multitude of design tools to choose from, many of which use guidelines that are based on animal experiments yet allow the use of plant genomes. Upon choosing sgRNAs, it is also unclear whether an in vitro assay is needed to validate the targeting efficiency of a particular sgRNA before in vivo delivery of the CRISPR/Cas9 system. Here, we demonstrate the in vitro and in vivo activity of four different sgRNAs that we selected based on their ability to target multiple members of the eggplant polyphenol oxidase gene family. Some sgRNAs that have high in vitro cleavage activity did not produce edits in vivo, suggesting that an in vitro assay may not be a reliable basis to predict sgRNAs with highly efficient in vivo cleavage activity. Further analysis of our sgRNAs using other design algorithms suggest that plant-validated criteria such as the presence of necessary secondary structures and appropriate base-pairing may be the reason for the discrepancy between our observed in vitro and in vivo cleavage efficiencies. However, recent reports and our data suggests that there is no guaranteed way to ensure the in vivo cleavage of chosen sgRNAs.

There are ongoing concerns of social justice regarding inequalities in the distribution of access to potential genome editing technologies. Working within non-ideal theory, Colin Farrelly advances a justification for the use of patents to speed up the arrival of safe and effective interventions for all, including the socially disadvantaged. This paper argues that such success is less assured when one considers the actual functioning of patents and the practical implications of the patent system in the context of biotechnological innovations. I suggest that non-ideal theoretical approaches risk reverting back to a form of ideal theory if they simply refer to such real-world constraints - e.g. patents - but do not critically assess and fully examine how such constraints manifest themselves in practice. I highlight some considerations that would be important in order to develop and foster a more robust non-ideal approach to justice in biotechnological developments.

Twins\' memoirs and autobiographies both enlighten and entertain. These works, often overlooked by researchers, may suggest new avenues for investigation, such as nonshared environmental events that propel twins in different directions. Of course, MZ twins\' generally parallel experiences and DZ twins generally criss-crossing paths are the bases of fascinating life stories. The following sections examined recent research on fetal reduction in twin pregnancy, twins\' personality and military service, growth restriction in twins, and advances in conjoined twin separation. This article closes with reports of a scientist who performed gene editing on twins, a twin conception from 33-year-old embryos, twins\' physical outcomes from dietary differences, fraternal twins with the world\'s largest height difference and the Twin Home Experts who conquer rat infestation in New York.

The Chinese government has issued a series of new policies to make it easier to industrialize gene-edited crops. However, whether technological advantages will eventually translate into industrial advantages and whether farmers will soon have access to gene-edited varieties partly depends on seed companies\' willingness to produce and sell gene-edited varieties to farmers and to invest in developing their own gene-edited varieties. This study utilizes data from a survey of 111 seed companies collected in 2019 before the implementation of new regulations. This study provides empirical evidence on whether gene-edited crops will be available to farmers. The results show that the number of companies conducting research on gene-edited crops is limited, mostly to large companies. Approximately 55% of seed company managers would consider developing and selling gene-edited crops modified by SDN-1 and SDN-2 site-directed nuclease genome editing without external genetic material, whereas 46% support crops modified by SDN-3, which require gene replacement or foreign deoxyribonucleic acid (DNA) insertion and are regulated as genetically modified organisms (GMOs). The regression results show that large companies and companies with well-educated researchers are more likely to support and develop gene-editing technology. Past GM investment experience and collaboration with public institutions in gene-editing research increases the probability of company investment in gene editing R&D. These results suggest that gene-edited cultivars are more likely to be produced and sold to farmers in the future than GMOs, and that gene-edited agricultural products could have a significant market share of the seed market in the future.

Complex biomolecular technologies revolutionise scientific research. Fully embedding scientific advances in the community requires innovative ways to educate learners on the molecular foundations upon which these technologies are based. In this case study, we present the conception and design of Walter and Eliza Hall Institute of Medical Research (WEHI\'s) inaugural wholly online learning course focussed on explaining the revolutionary genome-editing technology, clustered regulatory interspaced palindromic repeats (CRISPR). Utilising WEHI\'s strength in bringing science educators and world-leading CRISPR scientists together, we designed a multimodal online resource that introduces learners, without an extensive background in either science or genome editing, to the fundamental concepts of CRISPR technology. Using the online course creation tool, Articulate 360, we guided learners through three modules containing targeted lessons designed to focus on specific learning outcomes. Integrated videos, research articles, interviews, and other resources, allowed for self-paced learning that met various learning style needs. The extensive resources provided opportunities to delve deeper into the content for advanced learners. The effectiveness of the course, evaluated with survey responses collected upon completion of the course, highlighted the ease of use and functionality of the course, and an increased understanding of CRISPR technology after course completion. We anticipate future online learning course development to showcase complex molecular technology that will be valuable for tertiary education, as well as for those in the wider community interested in understanding important advances in biomedicine.

This article systematically discusses Chinese current legal status and rules for human embryo gene editing in both administrative law and criminal law after several legislative modifications, and further systematically evaluates the values and the defects of these modifications. After He Jiankui\'s case, Chinese legislators devoted themselves to improve human embryo gene editing legislation. As a result, human embryo gene editing\'s legal status becomes more determined. Rules for human embryo gene editing in Chinese administrative law have gradually become a complete system centering on \"CBL-regulation,\" and the promulgation of Amendment (XI) to the Criminal Law reconciles the controversy existed in academic circles. Chinese rules for human embryo gene editing are moving from \"doubtful development\" to \"complete legal system.\"

There are an estimated > 400 million people living with a rare disease globally, with genetic variants the cause of approximately 80% of cases. Next Generation Sequencing (NGS) rapidly identifies genetic variants however they are often of unknown significance. Low throughput functional validation in specialist laboratories is the current ad hoc approach for functional validation of genetic variants, which creating major bottlenecks in patient diagnosis. This study investigates the application of CRISPR gene editing followed by genome wide transcriptomic profiling to facilitate patient diagnosis. As proof-of-concept, we introduced a variant in the Euchromatin histone methyl transferase (EHMT1) gene into HEK293T cells. We identified changes in the regulation of the cell cycle, neural gene expression and suppression of gene expression changes on chromosome 19 and chromosome X, that are in keeping with Kleefstra syndrome clinical phenotype and/or provide insight into disease mechanism. This study demonstrates the utility of genome editing followed by functional readouts to rapidly and systematically validating the function of variants of unknown significance in patients suffering from rare diseases.

The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-mediated protein 9 (CRISPR-Cas9) immediately revealed numerous potential therapeutic applications. Although CRISPR-Cas9 will most likely be useful for addressing issues such as genetic diseases and related medical issues, use of this modality for germline modification generates complex ethical questions regarding the safety and efficacy, human genetic enhancement, and \"designer\" babies. In this article, the case of the He Jiankui affair is used as an example of the potential for unregulated use of CRISPR-Cas9 technology. In 2018, Dr He Jiankui reported that he had successfully edited human embryos. This work clearly violates all international principles of bioethics. As such, the purpose of this paper is to explore the ethical challenges inherent in the use of CRISPR-Cas9 for human germline editing from the perspectives of the goals of Islamic law (Maqasid al Shari\'a) and the major jurisprudential maxims (Qawaid Fiqhiyyah). We argue that from an Islamic standpoint, the therapeutic application of CRISPR-Cas9 for germline editing may be permissible if the safety and efficacy concerns are resolved and if the principles of Maqasid al-Shari\'a are fulfilled.