Vectorology - GEG Tech top picks
21.1K views | +1 today
Follow
Vectorology - GEG Tech top picks
Your new post is loading...
Your new post is loading...
Scooped by BigField GEG Tech
Scoop.it!

UK first to approve CRISPR treatments for diseases: what you need to know - Nature

UK first to approve CRISPR treatments for diseases: what you need to know - Nature | Vectorology - GEG Tech top picks | Scoop.it

The landmark decision could transform the treatment of sickle-cell disease and beta-thalassaemia — but the technology is expensive.

BigField GEG Tech's insight:

The landmark decision could transform the treatment of sickle-cell disease and beta-thalassaemia — but the technology is expensive.... and safe.....?

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Intranasal delivery of CRISPR/Cas9 therapeutics may help treat chronic anxiety

Intranasal delivery of CRISPR/Cas9 therapeutics may help treat chronic anxiety | Vectorology - GEG Tech top picks | Scoop.it
A study in mice reports a CRISPR/Cas9 gene-editing delivery system, capable of bypassing the blood-brain-barrier and modulating neuronal receptor pathways, to treat chronic anxiety.
BigField GEG Tech's insight:

A mouse study reports on a CRISPR/Cas9 gene-editing delivery system, capable of bypassing the blood-brain barrier and modulating neuronal receptor pathways, to treat chronic anxiety. Researchers targeted 5HT-2A, a serotonin receptor known to play a role in anxiety and depression. The authors used a vector based on an inactivated adeno-associated virus to deliver the vector via the nose. The vector delivers a guide RNA to the neurons. The guide RNA binds to the target receptor gene, HTR2A, which is then cleaved at a precise location by the Cas9 enzyme. Five weeks after intranasal administration of the vector and packaging, 75 mice were tested with standard behavioral tests measuring mouse anxiety. For example, anxious mice would choose to spend more time in dark areas and would tend to bury unfamiliar objects such as logs in sawdust rather than leave them alone. Treated mice spent 35.7% more time in light areas than controls and showed a 14.8% decrease in the number of logs buried compared to controls. Mice treated with the CRISPR package showed an 8.47-fold decrease in HTR2A expression in their brains, compared with control mice. According to the authors, non-invasive intranasal administration of CRISPR/Cas9 therapies may therefore help patients with treatment-resistant anxiety. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Efficient engineering of human and mouse primary cells using peptide-assisted genome editing | Nature Biotechnology

Efficient engineering of human and mouse primary cells using peptide-assisted genome editing | Nature Biotechnology | Vectorology - GEG Tech top picks | Scoop.it
Simple, efficient and well-tolerated delivery of CRISPR genome editing systems into primary cells remains a major challenge. Here we describe an engineered Peptide-Assisted Genome Editing (PAGE) CRISPR–Cas system for rapid and robust editing of primary cells with minimal toxicity. The PAGE system requires only a 30-min incubation with a cell-penetrating Cas9 or Cas12a and a cell-penetrating endosomal escape peptide to achieve robust single and multiplex genome editing. Unlike electroporation-based methods, PAGE gene editing has low cellular toxicity and shows no significant transcriptional perturbation. We demonstrate rapid and efficient editing of primary cells, including human and mouse T cells, as well as human hematopoietic progenitor cells, with editing efficiencies upwards of 98%. PAGE provides a broadly generalizable platform for next-generation genome engineering in primary cells. Peptide-assisted genome editing enables efficient single and multiplex editing in hematopoietic cells.
BigField GEG Tech's insight:

Current methods of getting CRISPR-Cas systems into cells, which include the use of carrier viruses and electric pulses, are inefficient for cells taken directly from patients, called primary cells. These methods also typically kill many of the cells they are used on, and can even cause broad unwanted changes in gene activity. In a new study, which appeared in Nature Biotechnology, researchers explored the use of small, virus-derived protein fragments, called peptides, to pilot CRISPR-Cas molecules more efficiently through the outer membranes of primary human cells and into their nuclei. Notably, researchers found that a fused combination of two modified peptides : one found in HIV and one in influenza viruses, could be mixed with CRISPR-Cas molecules to get them into primary human or mouse cells and their nuclei with efficiencies of up to nearly 100 percent, depending on the cell type and with almost no toxicity or gene-expression changes. The team demonstrated the approach, which they call peptide-assisted genome editing (PAGE), for several types of envisioned cell therapy including CAR T cell therapies. The scientists expect the new technique to be particularly useful for modifying T cells and other cells from a patient's own body to make cell therapies. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Applied Cells Inc. and GenScript enter strategic collaboration to deliver combined solutions for cell therapy development

Applied Cells Inc. and GenScript enter strategic collaboration to deliver combined solutions for cell therapy development | Vectorology - GEG Tech top picks | Scoop.it

November 18th, 2022. Today, Applied Cells Inc. and GenScript USA Incorporated announced their strategic collaboration to deliver combined cell isolation solutions for cell therapy drug development worldwide. Under this collaboration, GenScript will develop and supply its proprietary research and cGMP grade CytoSinct™ reagents for use in developing CAR-T and other Cell Therapy products on the Applied Cells MARS® Platform.

BigField GEG Tech's insight:

Applied Cells Inc. and GenScript USA Incorporated announced their strategic collaboration to provide combined cell isolation solutions for cell therapy drug development worldwide. As part of the collaboration, GenScript will develop and provide its proprietary research-grade cGMP CytoSinct™ reagents for use in the development of CAR-T and other cell therapy products on the Applied Cells MARS platform. The CytoSinct™ reagents use advanced nanoparticles, high-quality antibodies and optimized conjugation chemistry to enable high specificity and sensitivity in cell selection. The Applied Cells MARS ® platform uses proprietary column-free magnetic separation technology and provides an automated closed system for the cell selection process. The integration of CytoSinct™ reagents into the MARS ® platform provides a complete solution for streamlined workflow and high-efficiency results for industrial-scale cell research and separation. GenScript and Applied Cells will support GMP-compliant documentation for cell therapy products developed using this innovative solution. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4+ T cell immunity - Cell Rep

A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4+ T cell immunity - Cell Rep | Vectorology - GEG Tech top picks | Scoop.it
BigField GEG Tech's insight:

Lopez et al. show that lentiviral vaccination vectors encoding mycobacterial antigens attached to a component of a cellular antigen-presentation machinery display improved immunogenicity. Using antigens from Mycobacterium tuberculosis bacilli in this strategy, combined with intranasal vaccination, they observe protection potential against tuberculosis in mice.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

New platform for gene editing may change the landscape of CRISPR-based therapeutics

New platform for gene editing may change the landscape of CRISPR-based therapeutics | Vectorology - GEG Tech top picks | Scoop.it
A team of researchers at Northwestern University has devised a new platform for gene editing that could inform the future application of a near-limitless library of CRISPR-based therapeutics.
BigField GEG Tech's insight:

A team of researchers at Northwestern University has designed a new platform for gene editing. Using chemical design and synthesis, the team brought together CRISPR-Cas9 with a therapeutic technology born in their lab to overcome a critical limitation of the gene editing tool: its delivery. The team developed a way to transform the Cas-9 protein into a spherical nucleic acid (SNA) and load it with critical components as needed to access a wide range of tissue and cell types, as well as the intracellular compartments needed for gene editing. This study shows how CRISPR SNAs can be delivered across the cell membrane and into the nucleus while maintaining bioactivity and gene editing capabilities. The researchers used Cas9, a protein required for gene editing, as the core of the construct, and attached DNA strands to its surface to create a new type of SNA. In addition, these SNAs were preloaded with RNA capable of gene editing and fused with peptides to control their ability to navigate the compartmental barriers of the cell, maximizing efficiency.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Genome editing approaches enable precise gene correction and disease rescue in inherited retinal diseases

Genome editing approaches enable precise gene correction and disease rescue in inherited retinal diseases | Vectorology - GEG Tech top picks | Scoop.it
In a new paper, University of California, Irvine researchers explain how precision genome editing agents have enabled precise gene correction and disease rescue in inherited retinal diseases (IRDs).
BigField GEG Tech's insight:

In a new paper, researchers from the University of California explain how precision genome editing agents have enabled precise gene correction and rescue in inherited retinal diseases (IRD). The study "Precision Genome Editing in the Eye" was published in the Proceedings of the National Academy of Sciences. The article describes current preclinical successes and clinical approaches to genome editing for the treatment of inherited retinal degenerative diseases. According to the article, in vivo gene editing will be the future treatment paradigm for IRD. Currently, there is no effective treatment for these devastating diseases, which typically result in blindness. Over the past two decades, major advances in gene therapy have raised new hopes for the successful treatment of these IRDs. More recently, precision genome editing agents, including core and master editors, developed by The Liu Lab, have enabled efficient and precise correction of the target gene, rather than gene disruption, in a variety of therapeutic settings, including mouse models of IRD. Precise correction of the target gene greatly expands the potential therapeutic applications of genome editing technologies, as most genetic disorders cannot be treated by gene disruption.   

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Novel method for gene editing of hPSCs yields up to 84% knockout efficiency

Novel method for gene editing of hPSCs yields up to 84% knockout efficiency | Vectorology - GEG Tech top picks | Scoop.it
A Penn State-led team of interdisciplinary researchers has developed techniques to improve the efficiency of CRISPR-Cas9, the genome editing technique that earned the Nobel Prize in 2020.
BigField GEG Tech's insight:

Researchers have developed a more efficient and accessible process for applying CRISPR-Cas9 systems in human pluripotent stem cells (hPSCs) that could advance diagnoses and treatments for genetic disorders. To improve this system, the researchers changed the way the tool is delivered to stem cells, using modified RNA (modRNA). ModRNA differs from plasmid DNA in that it replaces one of the basic substrates found in RNA with a chemically modified version, and it is stabilized by a stronger structural support. About 90% of the cells received the modRNA from a single transfection. The researchers also found that the length of time the modRNA was in place was ideal: long enough to modify the cells, but not too long to cause off-target activity. However, when the Cas9 modRNA is successfully delivered to the target gene, it creates a double-stranded break in the genome, which some cells will try to repair and pass the repair, or "mutation," to their offspring. To reduce the toxic side effects of Cas9 and help the modified cells survive, the researchers also introduced a small protein known to help cells grow. This added protein inhibited cell death and improved the efficiency of Cas9 editing by up to 84%. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

New dual-plasmid editing system for DNA-based information rewriting in vivo

New dual-plasmid editing system for DNA-based information rewriting in vivo | Vectorology - GEG Tech top picks | Scoop.it
DNA-based information is a new interdisciplinary field linking information technology and biotechnology.
BigField GEG Tech's insight:

Despite DNA's promise of high stability, high storage density and low maintenance cost, researchers face problems in accurately rewriting the digital information encoded in DNA sequences. To solve the rewriting problem, the researchers established an in vivo double plasmid system using a rationally designed coding algorithm and an information editing tool. This dual-plasmid system is suitable for storing, reading, and rewriting various types of information, including text, codebooks and images. It fully explores the encoding capability of DNA sequences without the need for addressing indices or backup sequences. It is also compatible with various types of coding algorithms, allowing high coding efficiency. For example, the coding efficiency of the current system reaches 4.0 bits per nucleotide. To achieve high efficiency and reliability in rewriting complex information stored in exogenous DNA sequences in vivo, a variety of CRISPR-associated proteins (Cas) and recombinases were used. The information rewriting tool thus became highly adaptable to complex information, resulting in a rewriting reliability of up to 94%, which is comparable to existing gene editing systems. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

New DNA repair vehicle used to fix a common genetic cause of hereditary kidney disease

New DNA repair vehicle used to fix a common genetic cause of hereditary kidney disease | Vectorology - GEG Tech top picks | Scoop.it
Genetic mutations which cause a debilitating hereditary kidney disease affecting children and young adults have been fixed in patient-derived kidney cells using a potentially game-changing DNA repair-kit. The advance developed by University of Bristol scientists is published in Nucleic Acids Research.
BigField GEG Tech's insight:

Podocin is a protein normally located on the surface of specialized kidney cells and is essential for kidney function. The defective podocin, however, gets stuck inside the cell and never reaches the surface, permanently damaging the podocytes, a common genetic cause of inherited steroid-resistant nephrotic syndrome (SRNS). Gene therapy that repairs the genetic mutations that cause defective podocin offers hope to patients. However, current delivery systems that include lentiviruses, adenoviruses and adeno-associated viruses all share the same limitation in that they are limited in the space inside their viral shells and this in turn limits the amount of cargo they can deliver.  Applying synthetic biology techniques, the researchers therefore redesigned the baculovirus, a human-friendly insect virus that is no longer limited by cargo capacity. By creating a DNA repair kit, including the CRISPR/Cas 9 system and DNA sequences to replace the defective gene. The team delivered a single modified baculovirus with a healthy copy of the podocin gene together with the CRISPR/Cas machines to insert it with base-pair precision into the genome and this was able to reverse the pathogenic phenotype and restore podocin to the cell surface.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy

Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy | Vectorology - GEG Tech top picks | Scoop.it
We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gen
BigField GEG Tech's insight:

Many drugs cannot cross the blood-brain barrier (BBB), which also applies to most CRISPR-carrying vehicles. So Bingyang Shi made chemically functional nanocapsules to penetrate the BBB, according to a study recently published in Science Advances. He essentially packaged unique CRISPR-Cas9/sgRNA complexes in a coating consisting of a thin polymeric shell made of positively charged guanidine acrylate cross-linked with N,N-bis(acryloyl)cystamine that contains biodegradable disulfide bonds. The shell was finally decorated with the peptide angiopep-2. While coating rather than encapsulation was chosen to maintain the particle size at approximately 30 nm and thus facilitate BBB penetration, the angiopep-2 peptide served two purposes. It is a ligand that binds to low-density lipoprotein receptor-related protein-1, which is most highly expressed on BBB endothelial cells and glioblastoma (GBM) cells. This will result in the concentration of the nanocapsules around the BBB, increasing their chance of penetration into the brain, where they will then be preferentially taken up by GBMs. However, more work is needed before these nanocapsules can emerge as a therapy for GBM patients.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor | Nature Communications

Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor | Nature Communications | Vectorology - GEG Tech top picks | Scoop.it
Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option. The role of progesterone receptor (PR) and its interplay with estrogen receptor (ER) in breast cancer is controversial. Here, the authors demonstrate that PR can have an ER-independent role in breast cancer growth and metastasis and that its effects are dependent on MYC and androgen receptor signatures.
BigField GEG Tech's insight:

Proud to share one of our long-time partner's publication whom we have designed robust and efficient lentiviral vectors for its project in breast cancer.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates | Nature Communications

Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates | Nature Communications | Vectorology - GEG Tech top picks | Scoop.it
BigField GEG Tech's insight:

In this study the scientists developed lentiviral vectors, which integrate in the host cell genome, that achieve efficient liver gene transfer in mice, dogs and non-human primates, by intravenous delivery. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy | Nature Communications

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy | Nature Communications | Vectorology - GEG Tech top picks | Scoop.it
Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications. Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.
BigField GEG Tech's insight:

Despite the significant advances made in recent years, there are still a number of obstacles standing in the way of wider application of gene therapies. These include the efficient delivery of genetic material to target cells with minimal side effects using adeno-associated viral (AAV) vectors. AAV carriers have an advantageous safety profile and high gene transfer efficiency, which means they are often used in gene therapy and CRISPR/Cas gene editing. But AAVs have limited DNA uptake capacity and cannot reliably transport larger genes. A team of researchers has developed a new approach to overcome these drawbacks. This new method, dubbed REVeRT (reconstitution via mRNA trans-splicing), also uses the principle of dual AAV vectors. However, unlike previous technologies, it relies on the assembly of gene fragments divided at the transcriptional level. The team has already developed the method for ophthalmological applications in cell cultures, and has successfully evaluated it in animal models under a variety of conditions, for example to treat hereditary macular degeneration by gene therapy.  

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

‘It’s a vote for hope’: first gene therapy for muscular dystrophy nears approval, but will it work? - Nature

‘It’s a vote for hope’: first gene therapy for muscular dystrophy nears approval, but will it work? - Nature | Vectorology - GEG Tech top picks | Scoop.it
BigField GEG Tech's insight:

The FDA’s decision, expected this month, follows several setbacks and delays and will pose difficult choices for the families of children with Duchenne muscular dystrophy. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

FDA Approves First Gene Therapy for the Treatment of High-Risk, Non-Muscle-Invasive Bladder Cancer | FDA

FDA Approves First Gene Therapy for the Treatment of High-Risk, Non-Muscle-Invasive Bladder Cancer | FDA | Vectorology - GEG Tech top picks | Scoop.it
BigField GEG Tech's insight:

FDA approves Adstiladrin, a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

FDA approves the first Gene Therapy to Treat Adults with Hemophilia B which is the most expensive drug ever, $3.5 million-per-dose | FDA

FDA approves the first Gene Therapy to Treat Adults with Hemophilia B which is the most expensive drug ever, $3.5 million-per-dose | FDA | Vectorology - GEG Tech top picks | Scoop.it

FDA approves Hemgenix, an adeno-associated virus vector-based gene therapy indicated for treatment of adults with Hemophilia B (congenital Factor IX deficiency)

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

News: A GEENIE in a Bottle: CyGenica’s Unique Non-Viral Cargo Delivery Platform

News: A GEENIE in a Bottle: CyGenica’s Unique Non-Viral Cargo Delivery Platform | Vectorology - GEG Tech top picks | Scoop.it
Irish-Indian company CyGenica is on a mission to solve the huge challenge surrounding targeted intracellular delivery of gene-editing and other therapies. In just five years since the company was founded, the first clinical trials for cancer are in sight. Here, CEO and CSO Dr Nusrat Sanghamitra PhD tells us about how a persona
BigField GEG Tech's insight:

CyGenica is an Irish-Indian company founded in 2017 that specializes in novel cargo delivery technologies. The company has developed a non-viral, non-toxic platform called GEENIE to develop solutions for in vitro and in vivo delivery of drugs, gene editing components such as CRISPR-Cas9, and antibiotics. The GEENIE platform can be thought of as a protein drill that pierces the cell membrane and brings its cargo with it. It is a 48 KDa protein that is introduced into cells by a non-endocytic mechanism that does not damage the cells. It delivers its cargo to the nucleus, which is very relevant for gene editing therapies. For each target organ, researchers design the GEENIE platform separately to make it "go" to the right place in the body. This strategy works in vitro in HER2+ breast cancer and in glioblastoma. For each of these targets, a specific construct that recognizes a unique receptor on the target cells has been developed. This strategy can be applied to any tissue type as long as a unique receptor has been identified. Moreover, the researchers have so far administered GEENIE to animals by intravenous injection, but because this protein is so stable, they want to try to develop an inhalation method for lung treatments in the future.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Frontiers | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings

Frontiers | Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings | Vectorology - GEG Tech top picks | Scoop.it
Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene packaging capacities, off-target transduction, and immunogenicity. In this study, we analysed over two decades of AAV applications, in 136 clinical trials. This meta-analysis aims to provide an up-to-date overview of the use and successes of AAVs in clinical trials, while evaluating the approaches used to address the above challenges. First, this study reveals that the speed of novel AAV development has varied between therapeutic areas, with particular room for improvement in Central Nervous System disorders, where development has been slow. Second, the lack of dose-dependent toxicity and efficacy data indicates that optimal dosing regimes remain elusive. Third, more clinical data on the effectiveness of various immune-modulation strategies and gene editing approaches are required to direct future research and to accelerate the translation of AAV-mediated gene therapy into human applications.
BigField GEG Tech's insight:

Very comprehensive and good analysis highlighting issues and challenges about the AAV use in gene therapy. After reading, you might well think that the non-integrating lentiviral vectors could answer several issues relating to the use of AAV, it is a pity that this type of vector is underused, a lack of fame? Maybe combined with a conservative use of the first generations of vectors in gene therapy as illustrated through this article, pointing out several examples showing that the implementations of vectorology innovations in clinic take time.  

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

News: Prime Editing Can Become the Future of Vision Loss Treatment

News: Prime Editing Can Become the Future of Vision Loss Treatment | Vectorology - GEG Tech top picks | Scoop.it
Gene editing has revolutionised research and is set to change the treatment landscape for genetic diseases, with >100 ongoing clinical trials across diverse disease areas. Here, medical doctor Silja Hansen, who is currently a PhD student at Aarhus University in Denmark, discusses the promise, challenges, and future of prime editing t
BigField GEG Tech's insight:

Inherited retinal diseases are characterized by dysfunction and degeneration of the photoreceptors and/or the retinal pigment epithelium, leading to progressive vision loss and blindness. After winning a grant of just over DKK 3 million (EUR 400,000) from the Velux Foundation, PhD student Silja Hansen MD aims to develop a new treatment based on prime editing to slow the progression of inherited retinal diseases. This editing has the potential to correct all kinds of point mutations as well as smaller deletions and insertions that cover many of the variants underlying inherited retinal diseases. This tool functions as an all-in-one system thanks to the pegRNA that directs the enzyme complex to the target site and as its own template because it does not require a double-strand break. One of the challenges of prime editing is to find a pegRNA that can create the desired editing and achieve high targeting efficiency. Another major challenge is the delivery of the gene editing cargo. Previous studies have explored the possibility of using a dual adeno-associated virus to provide a split master editor system. They would like to test this strategy but would also like to investigate different delivery options, including non-viral delivery methods. 

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

News: CRISPR Gene Silencing Offers Hope for Ultra-Rare Muscular Dystrophies

News: CRISPR Gene Silencing Offers Hope for Ultra-Rare Muscular Dystrophies | Vectorology - GEG Tech top picks | Scoop.it
Patients with collagen VI-related disorders experience progressive and debilitating disease. New research findings from Spain’s Institut de Recerca Sant Joan de Déu (IRSJD) provides new hope for these diseases, demonstrating the power of CRISPR-Cas9 to silence a dominant negative mutation in patient fibroblasts.
BigField GEG Tech's insight:

Collagen VI-related dystrophies (COL6-RD) are caused by mutations in the COL6A1, COL6A2 and COL6A3 genes that encode the alpha chains of collagen VI, a key component of the extracellular matrix. The prevalent pathogenic mutation in COL6A1 is a single nucleotide substitution, where a glycine is replaced by an arginine in the N-terminus of the triple helix domain which affects the folding of the resulting protein, hindering the association of tetramers to create the necessary collagen VI microfibrils. Moreover, there is currently no effective treatment available for COL6-RD. However, a recent paper demonstrates the use of CRISPR-Cas9 gene editing to mitigate the pathogenic effects of a dominant negative mutation in the COL6A1 gene. Nevertheless, an obvious hurdle for this type of therapy is the delivery of CRISPR-Cas9 reagents to fibroblasts in vivo; successful editing of somatic tissues such as muscle remains a significant challenge in the broader field. The research team hopes that recent advances in several areas of CRISPR delivery vehicles, including muscle adeno-associated trophic virus vectors and tissue-specific nanoparticles, may be the answer.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport 

Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport  | Vectorology - GEG Tech top picks | Scoop.it
The oncostatic effects of melatonin correlate with increased reactive oxygen species (ROS) levels, but how melatonin induces this ROS generation is unknown. In the present study, we aimed t
BigField GEG Tech's insight:

Proud to share a publication of one of our partner. In this study, they used a very specific vector allowing the expression of the Alternative OXidase (AOX) from Ciona intestinalis.

This type of vector played a part about the in vitro and in vivo characterization of the melatonin effects on the reactive oxygen species (ROS) levels in cancer cells .

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence | Nature Communications

Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence | Nature Communications | Vectorology - GEG Tech top picks | Scoop.it
More than 70% of human breast cancers (BCs) are estrogen receptor α-positive (ER+). A clinical challenge of ER+ BC is that they can recur decades after initial treatments. Mechanisms governing latent disease remain elusive due to lack of adequate in vivo models. We compare intraductal xenografts of ER+ and triple-negative (TN) BC cells and demonstrate that disseminated TNBC cells proliferate similarly as TNBC cells at the primary site whereas disseminated ER+ BC cells proliferate slower, they decrease CDH1 and increase ZEB1,2 expressions, and exhibit characteristics of epithelial-mesenchymal plasticity (EMP) and dormancy. Forced E-cadherin expression overcomes ER+ BC dormancy. Cytokine signalings are enriched in more active versus inactive disseminated tumour cells, suggesting microenvironmental triggers for awakening. We conclude that intraductal xenografts model ER + BC dormancy and reveal that EMP is essential for the generation of a dormant cell state and that targeting exit from EMP has therapeutic potential. The study of tumour dormancy is limited by suitable in vivo models. Here the authors show that mammary intraductal breast cancer (BC) xenografts model estrogen receptor α-positive (ER+) BC dormancy and rapid metastatic progression characteristic of triple-negative (TN) BC. The dormant disseminated ER+ BC cells display characteristics of epithelial-mesenchymal plasticity and forced expression of E-cadherin allows them to overcome dormancy.
BigField GEG Tech's insight:

Once again, proud to share a high-quality publication of the Brisken Lab at the EPFL, one of our long-standing partners. Two publications in Nature in two months, Wow ! As you said Cathrin, “tons more to do together” !

I take the opportunity to introduce the next workshop organized by Cathrin Brisken about the Preclinical and Personalized Breast Cancer Research.

 

https://www.epfl.ch/labs/brisken-lab/preclinicalmodelcourse/

 

First publication: https://www.linkedin.com/posts/nicolas-grandchamp-ab169a19_estrogen-receptor-positive-breast-cancers-activity-6943209061161017345-7_5P?utm_source=share&utm_medium=member_desktop

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Evaluating the State of the Science for Adeno-Associated Virus (AAV) Integration: An Integrated Perspective - CellPress

Evaluating the State of the Science for Adeno-Associated Virus (AAV) Integration: An Integrated Perspective - CellPress | Vectorology - GEG Tech top picks | Scoop.it
On August 18, 2021, the American Society of Gene and Cell Therapy (ASGCT) hosted a virtual roundtable on adeno-associated virus (AAV) integration, fea…
BigField GEG Tech's insight:

The purpose of this white paper is to review the evidence of rAAV-related host genome integration in animal models and possible risks of insertional mutagenesis in patients. In addition, technical considerations, regulatory guidance and bioethics are discussed.

No comment yet.
Scooped by BigField GEG Tech
Scoop.it!

Gene therapy’s comeback: how scientists are trying to make it safer - Nature

Gene therapy’s comeback: how scientists are trying to make it safer - Nature | Vectorology - GEG Tech top picks | Scoop.it
Unwanted immune responses threaten to derail some gene therapies. But researchers are seeking ways to combat harmful inflammation.
BigField GEG Tech's insight:

It is a pity that non integrating lentiviral vectors are unknown or underused. This is not THE solution but in several cases, I think their use would be more relevant than AAVs use in term of immune response. The advancements of gene therapy will go through the design and development of complementary vector platforms.

No comment yet.