CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0048
Peter F R Mills
{"title":"Institutional Bioethics: From Critical Interdisciplinarity to Cosmopolitanism.","authors":"Peter F R Mills","doi":"10.1089/crispr.2025.0048","DOIUrl":"https://doi.org/10.1089/crispr.2025.0048","url":null,"abstract":"<p><p>Bioethical institutions around the world have recently evolved from their emergence as a response to the societal challenges posed by advances in life sciences and biotechnology. Over the past quarter century, there has been a shift toward greater interdisciplinarity and inclusivity, incorporating social sciences and public engagement into institutional bioethical practice. In this perspective, I examine the UK's Nuffield Council on Bioethics as a case study of critical interdisciplinarity, contrasting it with more instrumental normative approaches. I highlight the Nuffield Council's commitment to autonomous ethical inquiry, the problematization of foundational assumptions, and the development of a public-facing \"non-expert discourse of experts.\" The challenges faced by this model-including deriving positive normative conclusions, generalizing from situated reflection, and the ambivalent relationship with policymaking-emphasize the need for a globally resonant and action-oriented ethics to guide powerful scientific developments.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0058
Sheila Jasanoff, J Benjamin Hurlbut, Krishanu Saha, Jacob D Moses, Daniel Affsprung, Henry Austin, Françoise Baylis, John H Evans, Timothy Hunt, Douglas A Kysar, Laurence Lwoff, Peter Mills, Jahnavi Phalkey, Matthew H Porteus, O Carter Snead, Kaushik Sunder Rajan, Carrie D Wolinetz
{"title":"A Reset for Bioethics: A Statement from the Global Observatory for Genome Editing.","authors":"Sheila Jasanoff, J Benjamin Hurlbut, Krishanu Saha, Jacob D Moses, Daniel Affsprung, Henry Austin, Françoise Baylis, John H Evans, Timothy Hunt, Douglas A Kysar, Laurence Lwoff, Peter Mills, Jahnavi Phalkey, Matthew H Porteus, O Carter Snead, Kaushik Sunder Rajan, Carrie D Wolinetz","doi":"10.1089/crispr.2025.0058","DOIUrl":"https://doi.org/10.1089/crispr.2025.0058","url":null,"abstract":"<p><p>How should we govern our increasing power to intervene in the processes of life? Genome editing, especially of the human germline, has brought this question to the forefront of global debate. We must seek to rectify shortcomings of earlier deliberative approaches by setting aside a science-and-technology first approach; expanding the range of questions for deliberation; revisiting the distribution of innovation's benefits and risks; and reimagining the limits of research. This Perspective from the Organizing Committee of the 2025 Global Observatory for Genome Editing International Summit calls for a new social compact, recognizing and rendering accountable the constitutive role of science and technology in shaping the meaning of human life in the 21st century.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0057
Jane Qiu
{"title":"From 'Frankenstein Science' to Cosmopolitan Ethics: Overlooked Perspectives on the 'CRISPR Babies' Scandal.","authors":"Jane Qiu","doi":"10.1089/crispr.2025.0057","DOIUrl":"https://doi.org/10.1089/crispr.2025.0057","url":null,"abstract":"<p><p>In November 2018, Chinese biophysicist He Jiankui stunned the world by announcing that he had created the first genetically-modified babies. Is he a rogue scientist? What are the socio-cultural contexts that motivated him to commit an act widely regarded as morally indefensible? What does it say about Chinese bioethics? How should we determine whether it can ever be justified to permanently alter the human gene pool? This article highlights the global institutional failures that enabled this unfortunate episode, including the prevailing international scientific culture and the persistent Western bias against scientific work originated in the Global South. It calls for systemic efforts-including regulatory reforms, increased transparency, public engagement, and international cooperation-to strengthen ethics governance both within nations and across borders. Finally, it advocates for decolonizing bioethics, advancing the sociology of bioethics, and fostering a cosmopolitan approach to ethics grounded in diversity, equity, inclusion, and our shared humanity.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0060
Jacob D Moses, J Benjamin Hurlbut, Sheila Jasanoff, Krishanu Saha
{"title":"Introducing Perspectives from the Global Observatory for Genome Editing.","authors":"Jacob D Moses, J Benjamin Hurlbut, Sheila Jasanoff, Krishanu Saha","doi":"10.1089/crispr.2025.0060","DOIUrl":"https://doi.org/10.1089/crispr.2025.0060","url":null,"abstract":"","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0043
Stuart A Newman
{"title":"Opposing Human Genetic Engineering.","authors":"Stuart A Newman","doi":"10.1089/crispr.2025.0043","DOIUrl":"https://doi.org/10.1089/crispr.2025.0043","url":null,"abstract":"<p><p>The past five decades have been a time of substantial change in the technological capacity to modify genetic material. During this period, I have maintained an unwavering stance against human germline modification. As a biologist who has researched the complexities of genotype-phenotype relationships, I remain convinced embryo-stage human genetic modification will always remain in the realm of uncontrolled experimentation. Based on my observations and participation in the twists and turns of genetics and society, I point to the limits of calls for \"broad societal consensus.\"</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-05-21DOI: 10.1089/crispr.2025.0053
Sarojini Nadimpally, Keertana K Tella
{"title":"Recalibrating Health Governance, Equity, and Reproductive Rights in India: A Case Study from the Global South.","authors":"Sarojini Nadimpally, Keertana K Tella","doi":"10.1089/crispr.2025.0053","DOIUrl":"https://doi.org/10.1089/crispr.2025.0053","url":null,"abstract":"<p><p>This perspective addresses the question of reproductive governance and public health in India by drawing on experiences as a civil society organization in the field. We attempt to highlight some key issues that have emerged on this question in relation to reproductive rights, sickle cell disease management, and the ethical implications of technological advances, from the location of the Global South. In the discourse on cosmopolitan ethics, the emphasis should be on equity and social justice for marginalized people through a system that respects cultural diversity, combats systemic biases, and ensures patients' autonomy. We underscore the importance of multiple moral intuitions and notions of plurality as central to achieving health justice.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-04-01Epub Date: 2025-01-08DOI: 10.1089/crispr.2024.0093
Murat Buyukyoruk, Pushya Krishna, Andrew Santiago-Frangos, Blake Wiedenheft
{"title":"Discovery of Diverse CRISPR Leader Motifs, Putative Functions, and Applications for Enhanced CRISPR Detection and Subtype Annotation.","authors":"Murat Buyukyoruk, Pushya Krishna, Andrew Santiago-Frangos, Blake Wiedenheft","doi":"10.1089/crispr.2024.0093","DOIUrl":"10.1089/crispr.2024.0093","url":null,"abstract":"<p><p>Bacteria and archaea acquire resistance to genetic parasites by preferentially integrating short fragments of foreign DNA at one end of a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR). \"Leader\" DNA upstream of CRISPR loci regulates transcription and foreign DNA integration into the CRISPR. Here, we analyze 37,477 CRISPRs from 39,277 bacterial and 556 archaeal genomes to identify conserved sequence motifs in CRISPR leaders. A global analysis of all leader sequences fails to identify universally conserved motifs. However, an analysis of leader sequences that have been grouped by 16S rRNA-based taxonomy and CRISPR subtype reveals 87 specific motifs in type I, II, III, and V CRISPR leaders. Fourteen of these leader motifs have biochemically demonstrated roles in CRISPR biology including integration, transcription, and CRISPR RNA processing. Another 28 motifs are related to DNA binding sites for proteins with functions that are consistent with regulating CRISPR activity. In addition, we show that these leader motifs can be used to improve existing CRISPR detection methods and enhance the accuracy of CRISPR classification.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"137-148"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-04-01Epub Date: 2025-03-31DOI: 10.1089/crispr.2024.0100
Jesse Tordoff, Lauren E Alfonse, Kira S Makarova, Alexa Ornstein, Anthony J Garrity, Winston X Yan, David A Scott, Eugene V Koonin, David R Cheng
{"title":"Initial Characterization of 12 New Subtypes and Variants of Type V CRISPR Systems.","authors":"Jesse Tordoff, Lauren E Alfonse, Kira S Makarova, Alexa Ornstein, Anthony J Garrity, Winston X Yan, David A Scott, Eugene V Koonin, David R Cheng","doi":"10.1089/crispr.2024.0100","DOIUrl":"10.1089/crispr.2024.0100","url":null,"abstract":"<p><p>Type V CRISPR systems are highly diverse in sequence, mechanism, and function. Although recent efforts have greatly expanded our understanding of their evolution, the diversity of type V systems remains to be completely explored, and many clades have not been experimentally characterized. In this work, we mined metagenomic databases to identify three new subtypes and nine new variants of Cas12, the effector of Type V systems, and provide experimental and computational characterization of their Protospacer-Adjacent Motif (PAM), interference activity, loci architecture, and tracrRNA dependence. Half of the new Cas12s are found in phages or prophages. New subtypes Cas12o and Cas12p lack the canonical RuvC catalytic residues, suggesting they interfere with the target without cleavage, possibly by blocking transcription or replication. One variant, Cas12f10, displays substantial activity on PAM-less targets. Our work expands the diversity of the functionally characterized Cas12 effectors and provides some promising candidates for genome engineering tools.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"149-154"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-04-01Epub Date: 2025-04-02DOI: 10.1089/crispr.2024.0041
Agnes Kandlbinder, Marie-Hélène Peter-Spiess, Brigitte Leeners, Amina Mollaysa, Tommaso Cavazza, Anina Meier, Michael Braunschweig, Eleonora Ioannidi, Gerald Schwank, Michael Krauthammer
{"title":"Strategies for Interdisciplinary Human Gene Editing Research: Insights from a Swiss Project.","authors":"Agnes Kandlbinder, Marie-Hélène Peter-Spiess, Brigitte Leeners, Amina Mollaysa, Tommaso Cavazza, Anina Meier, Michael Braunschweig, Eleonora Ioannidi, Gerald Schwank, Michael Krauthammer","doi":"10.1089/crispr.2024.0041","DOIUrl":"10.1089/crispr.2024.0041","url":null,"abstract":"<p><p>CRISPR gene editing is a cutting-edge technology that has advanced tremendously in recent years. The first clinical CRISPR applications have been approved, and more gene editing therapies are to be expected in human medicine. Consequently, continuous basic research is needed to assess possibilities and prime future clinical applications. Because this technology not only offers new possibilities for treating diseases but also raises important ethical and societal questions, collaboration between human, life, biomedical, and medical sciences is needed. In this article, we discuss the practical challenges of such interdisciplinary projects and present strategies for addressing them based on our experience of conducting an interdisciplinary project on CRISPR. This work aims to help and encourage interdisciplinary collaborations and discussions on modern scientific endeavors that, such as gene editing, tend to blur the lines between traditional disciplines. The strategies suggested include realistic expectations, shared goals, space setting, and expert and lay dialogue.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"79-88"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CRISPR JournalPub Date : 2025-04-01Epub Date: 2025-03-31DOI: 10.1089/crispr.2024.0080
Eric A Noel, Srishti U Sahu, Stacia K Wyman, Netravathi Krishnappa, Chris Jeans, Ross C Wilson
{"title":"Hairpin Internal Nuclear Localization Signals in CRISPR-Cas9 Enhance Editing in Primary Human Lymphocytes.","authors":"Eric A Noel, Srishti U Sahu, Stacia K Wyman, Netravathi Krishnappa, Chris Jeans, Ross C Wilson","doi":"10.1089/crispr.2024.0080","DOIUrl":"10.1089/crispr.2024.0080","url":null,"abstract":"<p><p>The incorporation of nuclear localization signal (NLS) sequences at one or both termini of CRISPR enzymes is a widely adopted strategy to facilitate genome editing. Engineered variants of CRISPR enzymes with diverse NLS sequences have demonstrated superior performance, promoting nuclear localization and efficient DNA editing. However, limiting NLS fusion to the CRISPR protein's termini can negatively impact protein yield <i>via</i> recombinant expression. Here we present a distinct strategy involving the installation of hairpin internal NLS sequences (hiNLS) at rationally selected sites within the backbone of CRISPR-Cas9. We evaluated the performance of these hiNLS Cas9 variants by editing genes in human primary T cells following the delivery of ribonucleoprotein enzymes <i>via</i> either electroporation or co-incubation with amphiphilic peptides. We show that hiNLS Cas9 variants can improve editing efficiency in T cells compared with constructs with terminally fused NLS sequences. Furthermore, many hiNLS Cas9 constructs can be produced with high purity and yield, even when these constructs contain as many as nine NLS. These hiNLS Cas9 constructs represent a key advance in optimizing CRISPR effector design and may contribute to improved editing outcomes in research and therapeutic applications.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"105-119"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}