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Found: 26 174
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Gene Editing Approaches against Viral Infections and Strategy to Prevent Occurrence of Viral Escape.
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An Idea to Explore: Enhancing the Teaching of Genome Editing Through 3D Printed Models of CRISPR-Cas9 Technology.
Innovative biological discoveries are crucial for addressing global challenges, yet teaching these complex concepts poses significant difficulties due to the complexity of the subject matter as well as limited educational resources and methodologies. Genome editing, specifically with CRISPR-Cas9, represents a convergence of technology, molecular biology, and engineering, enabling precise manipulation of DNA sequences in various organisms. It leverages advanced tools and a deep understanding of molecular biology to target specific genes while applying engineering principles to improve editing mechanisms. However, the complexity of this field poses educational challenges due to a scarcity of accessible resources. To enhance the accessibility of genome editing to scientists and students, we propose utilizing 3D modeling and printing to create tangible models of key components in the genome editing process. By visualizing these molecular structures, our goal is to simplify and enrich the educational experience, making the intricate principles of genome editing more comprehensible and engaging for students.
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Angels and Devils: Dilemmas in Dual-Use Biotechnology.
Dual-use research, which results in knowledge that can be used for both good and ill, has become increasingly accessible in the internet age to both scientists and the general public. Here, we outline some major milestones for dual-use policy and present three vignettes that highlight contemporary dual-use issues in biotechnology.
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Induced Pluripotent Stem Cells and CRISPR-Cas9 Innovations for Treating Alpha-1 Antitrypsin Deficiency and Glycogen Storage Diseases.
Human induced pluripotent stem cell (iPSC) and CRISPR-Cas9 gene-editing technologies have become powerful tools in disease modeling and treatment. By harnessing recent biotechnological advancements, this review aims to equip researchers and clinicians with a comprehensive and updated understanding of the evolving treatment landscape for metabolic and genetic disorders, highlighting how iPSCs provide a unique platform for detailed pathological modeling and pharmacological testing, driving forward precision medicine and drug discovery. Concurrently, CRISPR-Cas9 offers unprecedented precision in gene correction, presenting potential curative therapies that move beyond symptomatic treatment. Therefore, this review examines the transformative role of iPSC technology and CRISPR-Cas9 gene editing in addressing metabolic and genetic disorders such as alpha-1 antitrypsin deficiency (A1AD) and glycogen storage disease (GSD), which significantly impact liver and pulmonary health and pose substantial challenges in clinical management. In addition, this review discusses significant achievements alongside persistent challenges such as technical limitations, ethical concerns, and regulatory hurdles. Future directions, including innovations in gene-editing accuracy and therapeutic delivery systems, are emphasized for next-generation therapies that leverage the full potential of iPSC and CRISPR-Cas9 technologies.
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Development of a quinic acid-induced CRISPR/Cas9 genome editing system and its application for the activation of ilicicolin H biosynthesis in Trichoderma reesei.
The CRISPR/Cas9 genome editing tool has been extensively utilized in filamentous fungi, including Trichoderma reesei. However, most existing systems employ constitutive promoters for the expression of Cas9 protein within the cells or directly introduce Cas9 protein into the cells, which often leads to continuous expression of Cas9 resulting in undesired phenotypes or increased operational cost. In this study, we identified a quinic acid (QA)-induced qai5 promoter and employed it to express Cas9, thereby establishing an inducible genome editing system in T. reesei. By utilizing this system, we successfully edited the ypr1 gene and the silent gene cluster involved in ilicicolin H synthesis using donor DNA labeling 41-bp homology arm (HA), resulting in an editing efficiency ranging from 29.2 % to 46.7 %. Consequently, biosynthesis of ilicicolin H was achieved in T. reesei. To summarize, this study presents a novel form of CRISPR/Cas9 genome editing system that enables efficient and controllable genetic modifications in T. reesei.
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Hypersymbiotics™: An artistic reflection on the ethical and environmental implications of microbiome research and new technologies.
This essay describes my ongoing series "Hypersymbiotics™," which began in 2012 and explores the potential ways in which our microbiome, genetics, epigenetics and even our environment could potentially be enhanced to turn us into human 'super-organisms.' The series includes performances and installations involving BioArt, as well as photographic documentation of ephemeral artworks and takes the form of a vehicle for public discussion about new healthcare technologies. The essay discusses artworks made using synthetic biology techniques including CRISPR genetic modification in bacteria and yeasts, and gene editing in plants, as well as using artificial intelligence and stem cell research. It critiques the role of the media and advertising in the promotion of complex new biomedical technologies. The "Hypersymbiotics™" series is deeply concerned with promoting public understanding of the ethical implications of new scientific developments and enabling reflection and debate. At its core the artwork is about knowledge, power, and control and where that resides.
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Targeting Specificity of the CRISPR/Cas9 System.
CRISPR/Cas9 system has accelerated research across many fields since its demonstration for genome editing. CRISPR also offers vast therapeutic potential, but an important hurdle of this technology is the off-target mutations it can induce. In this viewpoint, we will discuss recent strategies for improving CRISPR specificity, emphasizing how a complete mechanistic understanding of CRISPR/Cas9 can benefit such efforts. We also propose that agreeing upon a consensus protocol with the highest specificity could benefit researchers working on CRISPR-based therapies. In addition to improving CRISPR/Cas9 specificity, accurate detection of off-target events is also crucial, and we will discuss various unbiased off-target detection methods in terms of their advantages and disadvantages. We suggest that using a combination of cell-based and cell-free methods can prove more useful. In addition, we point out that improving predictive algorithms for off-target sites would require pooling of the available off-target analysis data and standardization of the protocols used for obtaining the data. Moreover, we highlight the risk of insertional mutagenesis for gene correction applications requiring the use of donor DNA. We conclude by discussing future prospects for the field, as well as steps that can be taken to overcome the aforementioned challenges.
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Targeted genome regulation via synthetic programmable transcriptional regulators.
Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications.
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A Consensus Model of Homology-Directed Repair Initiated by CRISPR/Cas Activity.
The mechanism of action of ssODN-directed gene editing has been a topic of discussion within the field of CRISPR gene editing since its inception. Multiple comparable, but distinct, pathways have been discovered for DNA repair both with and without a repair template oligonucleotide. We have previously described the ExACT pathway for oligo-driven DNA repair, which consisted of a two-step DNA synthesis-driven repair catalyzed by the simultaneous binding of the repair oligonucleotide (ssODN) upstream and downstream of the double-strand break. In order to better elucidate the mechanism of ExACT-based repair, we have challenged the assumptions of the pathway with those outlines in other similar non-ssODN-based DNA repair mechanisms. This more comprehensive iteration of the ExACT pathway better described the many different ways where DNA repair can occur in the presence of a repair oligonucleotide after CRISPR cleavage, as well as how these previously distinct pathways can overlap and lead to even more unique repair outcomes.
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Microinjection of the CRISPR/Cas9 editing system through the germ pore of a wheat microspore induces mutations in the target Ms2 gene.
BACKGROUND: Microinjection is a direct procedure for delivering various compounds via micropipette into individual cells. Combined with the CRISPR/Cas9 editing technology, it has been used to produce genetically engineered animal cells. However, genetic micromanipulation of intact plant cells has been a relatively unexplored area of research, partly due to the cytological characteristics of these cells. This study aimed to gain insight into the genetic micromanipulation of wheat microspores using microinjection procedures combined with the CRISPR/Cas9 editing system targeting the Ms2 gene. METHODS AND RESULTS: Microspores were first reprogrammed by starvation and heat shock treatment to make them structurally suitable for microinjection. The large central vacuole was fragmented and the nucleus with cytoplasm was positioned in the center of the cell. This step and an additional maltose gradient provided an adequate source of intact single cells in the three wheat genotypes. The microcapillary was inserted into the cell through the germ pore to deliver a working solution with a fluorescent marker. This procedure was much more efficient and less harmful to the microspore than inserting the microcapillary through the cell wall. The CRISPR/Cas9 binary vectors injected into reprogrammed microspores induced mutations in the target Ms2 gene with deletions ranging from 1 to 16 bp. CONCLUSIONS: This is the first report of successful genome editing in an intact microspore/wheat cell using the microinjection technique and the CRISPR/Cas9 editing system. The study presented offers a range of molecular and cellular biology tools that can aid in genetic micromanipulation and single-cell analysis.
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