RESUMEN
In vivo inactivation of a deleterious gene has been achieved in a small trial, with excellent clinical results. Interestingly, the delivery and editing system is the same as in previous work on a different disease, and the new therapy required simply changing the guide RNA used to target the Cas9 nuclease. This modular approach could be extended to a number of other genetic diseases.
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Sistemas CRISPR-Cas , Terapia Genética , Terapia Genética/métodos , Terapia Genética/tendencias , Humanos , Animales , Edición Génica/métodos , Edición Génica/tendencias , ARN Guía de Sistemas CRISPR-Cas/genética , Enfermedades Genéticas Congénitas/terapia , Enfermedades Genéticas Congénitas/genética , Técnicas de Transferencia de GenAsunto(s)
Sistemas CRISPR-Cas , Vacunas contra el Cáncer , Edición Génica , Neoplasias , Medicina de Precisión , Investigadores , Humanos , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Edición Génica/tendencias , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/genética , Medicina de Precisión/métodos , Medicina de Precisión/tendenciasAsunto(s)
Sistemas CRISPR-Cas , Ensayos Clínicos como Asunto , Edición Génica , Edición de ARN , ARN , Humanos , Ensayos Clínicos como Asunto/legislación & jurisprudencia , Ensayos Clínicos como Asunto/normas , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Edición Génica/tendencias , ARN/genética , Edición de ARN/genéticaRESUMEN
Precision genome editing is a rapidly evolving field in gene therapy, allowing for the precise modification of genetic material. The CRISPR and Cas systems, particularly the CRISPRCas9 system, have revolutionized genetic research and therapeutic development by enabling precise changes like single-nucleotide substitutions, insertions, and deletions. This technology has the potential to correct disease-causing mutations at their source, allowing for the treatment of various genetic diseases. Programmable nucleases like CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), and zinc finger nucleases (ZFNs) can be used to restore normal gene function, paving the way for novel therapeutic interventions. However, challenges, such as off-target effects, unintended modifications, and ethical concerns surrounding germline editing, require careful consideration and mitigation strategies. Researchers are exploring innovative solutions, such as enhanced nucleases, refined delivery methods, and improved bioinformatics tools for predicting and minimizing off-target effects. The prospects of precision genome editing in gene therapy are promising, with continued research and innovation expected to refine existing techniques and uncover new therapeutic applications.
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Sistemas CRISPR-Cas , Edición Génica , Terapia Genética , Humanos , Terapia Genética/métodos , Terapia Genética/tendencias , Edición Génica/métodos , Edición Génica/tendencias , Nucleasas con Dedos de Zinc/genética , Nucleasas de los Efectores Tipo Activadores de la Transcripción/genética , Medicina de Precisión/métodosAsunto(s)
Enfermedad de Alzheimer , Sistemas CRISPR-Cas , Edición Génica , Terapia Genética , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Edición Génica/tendencias , Terapia Genética/métodos , Terapia Genética/tendencias , MutaciónAsunto(s)
Anemia de Células Falciformes , Sistemas CRISPR-Cas , Edición Génica , Talasemia beta , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Talasemia beta/genética , Talasemia beta/terapia , Sistemas CRISPR-Cas/genética , Edición Génica/economía , Edición Génica/legislación & jurisprudencia , Edición Génica/tendencias , Reino Unido , HumanosRESUMEN
IMPORTANCE: The essential steps of successful gene delivery by recombinant adeno-associated viruses (rAAVs) include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene WDR63, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.
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Bronquios , Dependovirus , Epitelio , Técnicas de Transferencia de Gen , Vectores Genéticos , Transducción Genética , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , ADN , Epitelio/metabolismo , Epitelio/virología , Técnicas de Transferencia de Gen/tendencias , Terapia Genética/métodos , Vectores Genéticos/genética , Bronquios/metabolismo , Bronquios/virología , Transporte Activo de Núcleo Celular , Edición Génica/tendenciasAsunto(s)
Sistemas CRISPR-Cas , Camelus , Bovinos , Clonación de Organismos , Edición Génica , Ovinos , Animales , Bovinos/genética , Camelus/genética , Clonación de Organismos/tendencias , Clonación de Organismos/veterinaria , Sistemas CRISPR-Cas/genética , Edición Génica/tendencias , Edición Génica/veterinaria , Ovinos/genéticaRESUMEN
The present work has the objective of analyzing whether the practice of gene editing, from the teleological foundation, can generate a scenario of neoeugenic choices. This study analyzes the current stage of gene editing, together with the panorama of neoeugenic practices, to delimit the distinctive aspects between these concepts, based on the desired purpose in the practice of gene editing. For that, the analytical-discursive method was used, identifying fundamental connections related to the problem and interpreting the concepts presented in search of an adequate response to the objectives raised. The research was based on scientific articles published in specialized journals, as well as books and chapters in collective works. (AU)
El presente trabajo tiene como objetivo analizar si la práctica de la edición genética, desde el fundamento teleológico, puede generar un escenario de elecciones neoeugenésicas. Este estudio analiza la etapa actual de la edición de genes, junto con el panorama de las prácticas neoeugenésicas, con el fin de delimitar los aspectos distintivos entre estos conceptos, en función de la finalidad deseada en la práctica de la edición de genes. Para ello se utilizó el método analítico-discursivo, identificando conexiones fundamentales relacionadas con el problema e interpretando los conceptos presentados en busca de una respuesta adecuada a los objetivos planteados. La investigación se basó en artículos científicos publicados en revistasespecializadas, así como en libros y capítulos de obras colectivas. (AU)
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Humanos , Edición Génica/ética , Edición Génica/legislación & jurisprudencia , Edición Génica/tendencias , Discusiones Bioéticas/legislación & jurisprudencia , Genoma Humano/genética , Biotecnología/legislación & jurisprudenciaRESUMEN
This Medical News article is an interview with conference chair Manesh Patel, MD, chief of cardiology at the Duke University School of Medicine.
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COVID-19 , Cardiología , Edición Génica , Triglicéridos , Humanos , American Heart Association , Edición Génica/tendenciasRESUMEN
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR-Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
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Sistemas CRISPR-Cas , Tecnología de Genética Dirigida/métodos , Edición Génica/métodos , Genética de Población/métodos , ARN Guía de Kinetoplastida/genética , Alelos , Animales , Tecnología de Genética Dirigida/tendencias , Edición Génica/tendencias , Humanos , Modelos Genéticos , Mutación , ARN Guía de Kinetoplastida/metabolismoRESUMEN
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its associated proteins (Cas) is an adaptive immune system in archaea and most bacteria. By repurposing these systems for use in eukaryote cells, a substantial revolution has arisen in the genome engineering field. In recent years, CRISPR-Cas technology was rapidly developed and different types of DNA or RNA sequence editors, gene activator or repressor, and epigenome modulators established. The versatility and feasibility of CRISPR-Cas technology has introduced this system as the most suitable tool for discovering and studying the mechanism of specific genes and also for generating appropriate cell and animal models. SOX genes play crucial roles in development processes and stemness. To elucidate the exact roles of SOX factors and their partners in tissue hemostasis and cell regeneration, generating appropriate in vitro and in vivo models is crucial. In line with these premises, CRISPR-Cas technology is a promising tool for studying different family members of SOX transcription factors. In this review, we aim to highlight the importance of CRISPR-Cas and summarize the applications of this novel, promising technology in studying and decoding the function of different members of the SOX gene family.