Oxford Nanopore Technologies’ Post

Weren't able catch us at #ASGCT2024? You can still learn about our applications in cell and gene therapy research directly from Victor Weigman, PhD., in our on-demand webinar as he explores a method for achieving single-cell resolution in whole genome sequencing (WGS) with sufficient accuracy and precision to call single-nucleotide, copy-number, and structural variations resulting from off-target CRISPR/Cas9 activity. 👉 View on-demand: https://lnkd.in/gn8Y45cV The webinar covers: • PTA chemistry, found in ResolveDNA®, provides robust and precise whole genome sequencing data at the single-cell level. • Off-target genetic changes following CRISPR/Cas9 gene editing are highly variable and extensive. • Intercellular variability is common in on- and off-target editing events and should be considered when using bulk sequencing as a confirmation step. #CellTherapy #GeneTherapy #CGT #WGS #CRISPR

Molecular mechanisms of new gene-editing tool revealed Joint research determined the spatial structure of various processes of a novel gene-editing tool called “prime editor.” Functional analysis based on these structures also revealed how a “prime editor” could achieve reverse transcription, synthesizing DNA from RNA, without “cutting” both strands of the double helix. Clarifying these molecular mechanisms contributes greatly to designing gene-editing tools accurate enough for gene therapy treatments. The researchers succeeded in determining the three-dimensional structure of the prime editor complex in multiple states during reverse transcription on the target DNA. The structures revealed that the reverse transcriptase bound to the RNA–DNA complex that formed along the “part” of the Cas9 protein associated with DNA cleavage, the splitting of a single strand of the double helix. While performing the reverse transcription, the reverse transcriptase maintained its position relative to the Cas9 protein. The structural and biochemical analyses also indicated that the reverse transcriptase could lead to additional, undesired insertions. #ScienceMission #sciencenewshighlights https://lnkd.in/gnRw6EDj

Junk DNA in birds may hold key to safe, efficient gene therapy https://buff.ly/3UPAe4D #biotech #microbiology #biochemistry #research

Joint research led by Yutaro Shuto, Ryoya Nakagawa, and Osamu Nureki of the University of Tokyo determined the spatial structure of various processes of a novel gene-editing tool called "prime editor." Functional analysis based on these structures also revealed how a "prime editor" could achieve reverse transcription, synthesizing DNA from RNA, without "cutting" both strands of the double helix. Clarifying these molecular mechanisms contributes greatly to designing gene-editing tools accurate enough for gene therapy treatments. The findings are published in the journal Nature. Structural basis for pegRNA-guided reverse transcription by the prime editor, Nature (2024). DOI: 10.1038/s41586-024-07497-8 , https://lnkd.in/dZNYBHtP

The gene therapy field is constantly seeking out cost-effective and large-scale production of gene therapy vectors that are essential for treating genetic diseases. One aspect of vector production is understanding the molecular and cellular responses that can ultimately improve the effectiveness of gene therapy treatments. Dr. Alok Patra, PhD PMP, Dr Evan Tan, Dr Yee Jiun Kok, Associate Professor Ng Say Kong and Associate Professor Xuezhi Bi at #BTI have uncovered the underlying cellular mechanism governing recombinant adeno-associated viruses (rAAVs) production in HEK293 cells. rAAVs have become the preferred choice in gene therapy due to their efficient delivery with minimal side effects. By employing Sequential Window Acquisition of All Theoretical Fragment Ion Spectra (SWATH-MS) proteomics, unique expression patterns under 3 different conditions were mapped during rAAV production over a period of 72 hours. These findings will provide valuable insights into the cellular processes involving high titre rAAVs manufacturing, providing a more efficient and productive gene therapy treatment at an affordable cost for patients. Find out more about these exciting findings here: https://lnkd.in/giKyAp4f Come work with us: https://lnkd.in/gRU66bP #ASTAR #ASTARBTI #CreatingGrowth #EnhancingLives #Genetherapy

16S Ribosomal RNA Gene Sequencing‼️ Sequencing of a component of the prokaryotic ribosome 30S subunit, 16S ribosomal RNA (rRNA), which is one of the most conserved sequences over the course of evolution in prokaryotic organisms. Molecular 16S rRNA gene sequencing can support both diagnosis and the monitoring of treatment response; it has a greater sensitivity than culture and a higher specificity than other serologic methods. 16S rRNA gene sequencing is preferred for molecular detection and can support genus-to-species–level discrimination when more than 1000 base pairs of sequence can be obtained.

🎉Exciting news from our lab! We've explored how gene activity is influenced by DNA folding within 3D space, specifically within chromatin structures known as topologically associated domains (TADs). 🔺 We found that change in DNA folding can impact gene activity, but interestingly, this effect is limited to specific cell types. Though spatial organization of a locus generally remains the same across different cell types, minor spatial organization variations are connected to unique regulation pattern specific for a cell type. And gene activity is dependent on these tissue-specific feature. Dive into the full story here: https://lnkd.in/e8SyewTS This research is particularly exciting to me as it represents a major milestone in my PhD journey and is the first paper where I was fully involved ✨

Synthetic Biology and AAV! Really informative visit to Pall-Cytiva Portsmouth this week with my excellent doctoral student colleagues, Mehtap BAL and Qiantong（Tina） C. to discuss the application of synthetic biology to gene therapy AAV (adeno-associated virus) vector scale up. AAV has emerged as a leading gene therapy delivery platform, with several AAV-based therapies already approved and many more in the pipeline. AAV can package a wide range of genetic payloads, from small transgenes to large gene cassettes, has shown excellent safety and efficacy profiles in clinical trials and can achieve long-term transgene expression in target tissues. But there's still a lot of room for improvement. That's where synthetic biology comes in. With the power of synthetic biology behind it, I'm confident we'll see AAV technologies continue to advance and enable new breakthroughs in treating genetic diseases. #GeneTherapy #SyntheticBiology #AAV #GeneTech

Cre-loxP recombination has revolutionized genetic manipulation. The utility of Cre-loxP extends far and wide, revolutionizing gene therapy, functional genomics, and developmental biology. Early pioneers of conditional gene targeting, Klaus Rajewsky at Max Delbrück Center and Jamey Marth at Sanford Burnham Prebys, described the early days of transgenic mice. Andrew McMahon from the University of Southern California and Stefan Hans from Technische Universität Dresden shared how they built upon this technology. Read more about the foundational history of this technology: https://ow.ly/zczC50Qyw4u

Using the Gene Ontology to Annotate Key Players in Parkinson’s Disease Here we introduce the Parkinson’s disease GO Annotation Project, funded by Parkinson’s UK and supported by the GO Consortium, which is addressing this deficit by providing GO annotation to Parkinson’s-relevant human gene products, principally through expert literature curation. We discuss the steps taken to prioritise proteins, publications and cellular processes for annotation, examples of how GO annotations capture Parkinson’s-relevant information, and the advantages that a topic-focused annotation approach offers to users. Building on the existing GO resource, this project collates a vast amount of Parkinson’s-relevant literature into a set of high-quality annotations to be utilized by the research community. Keywords: #Annotation, #database; #Functional annotation; #Gene ontology; #High-throughput analysis; #Parkinson’s disease