Search results for "Cas9"
showing 10 items of 26 documents
In vitro genome editing using CRISPR/Cas9 to edit SERPINA1 PiZ mutation
2019
Introduction: The emergence some years ago of the CRISPR/Cas9 system allowed gene therapy to be specific, versatile, cheap and approachable to almost every laboratory. Due to these features, many different genetic diseases such as cystic fibrosis or β-thalassemia have been addressed in cellular models using the CRISPR/Cas9 genetic editing tool. Alpha-1 antytripsin deficiency (AATD) is a rare genetic condition that can provoke respiratory and hepatic symptoms. The Z allele of SERPINA1 gene is a well-characterised point mutation that can trigger the whole pathology. Henceforth, Z mutation is a suitable target for genetic edition using CRISPR/Cas9 in order to develop a gene therapy to treat AA…
Biochemical and Immunological implications of Lutein and Zeaxanthin
2021
Throughout history, nature has been acknowledged for being a primordial source of various bioactive molecules in which human macular carotenoids are gaining significant attention. Among 750 natural carotenoids, lutein, zeaxanthin and their oxidative metabolites are selectively accumulated in the macular region of living beings. Due to their vast applications in food, feed, pharmaceutical and nutraceuticals industries, the global market of lutein and zeaxanthin is continuously expanding but chemical synthesis, extraction and purification of these compounds from their natural repertoire e.g., plants, is somewhat costly and technically challenging. In this regard microbial as well as microalga…
Broadening the phenotypic spectrum and physiological insights related toEIF2S3variants
2021
Mental deficiency, epilepsy, hypogonadism, microcephaly and obesity (MEHMO) syndrome is a severe X-linked syndrome caused by pathogenic variants in EIF2S3. The gene encodes the γ subunit of the eukaryotic translation initiation factor-2, eIF2, essential for protein translation. A recurrent frameshift variant is described in severely affected patients while missense variants usually cause a moderate phenotype. We identified a novel missense variant (c.433A>G, p.(Met145Val)) in EIF2S3 in a mildly affected patient. Studies on zebrafish confirm the pathogenicity of this novel variant and three previously published missense variants. CRISPR/Cas9 knockout of eif2s3 in zebrafish embryos recapitula…
The plants of the future. : genome editing in biotechnology
2021
The evolution of life has led to the formation of complex systems where plants are essentials. Homo sapiens’ success is based on its ability to obtain food. In what remains of this century, the world population will increase by a quarter of the current total, reaching 10 billion people. This is itself a major challenge, amplified by the environmental conditions resulting from global change and the threat to sustainability derived from the use of the planet’s natural resources. Thus, we wonder if we will be able to respond to this challenge and, to that end, how the plants of the future should look. Recent advances in sequencing techniques allow us to identify genomes at a low cost, and geno…
Nanoscale delivery of phytochemicals targeting CRISPR/Cas9 for cancer therapy.
2021
Abstract Background With growing global prevalence, cancer is a major cause of disease-related deaths. The understanding of the fundamental tumor pathology has contributed to the development of agents targeting oncogenic signaling pathways. Although these agents have increased survival for defined cancers, the therapeutic choices are still limited due to the development of drug resistance. CRISPR/Cas9 is a powerful new technology in cancer therapy by facilitating the identification of novel treatment targets and development of cell-based treatment strategies. Purpose We focused on applications of the CRISPR/Cas9 system in cancer therapy and discuss nanoscale delivery of cytotoxic phytochemi…
Deploying Genome Editing Tools for Dissecting the Biology of Nut Trees
2019
Walnuts are among the most important nut crops grown in temperate regions of the world. Commercial production in California, and increasingly worldwide, relies on only few clonally grafted scion genotypes, particularly “Chandler,” and more recently clonally propagated disease-resistant rootstocks. Diseases, nematodes, insect pests, abiotic stresses, and other nutritional and environmental factors, can reduce walnut productivity and quality, affecting grower profitability. The California Walnut Breeding Program at UC Davis has developed and released scion cultivars and rootstocks to help address some of these problems. Sequencing of the walnut genome is expected to speed walnut breeding by f…
Zebrafish as a Model to Evaluate a CRISPR/Cas9-Based Exon Excision Approach as a Future Treatment Option for EYS-Associated Retinitis Pigmentosa
2021
Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) with an overall prevalence of 1 in 4000 individuals. Mutations in EYS (Eyes shut homolog) are among the most frequent causes of non-syndromic autosomal recessively inherited RP and act via a loss-of-function mechanism. In light of the recent successes for other IRDs, we investigated the therapeutic potential of exon skipping for EYS-associated RP. CRISPR/Cas9 was employed to generate zebrafish from which the region encompassing the orthologous exons 37-41 of human EYS (eys exons 40-44) was excised from the genome. The excision of these exons was predicted to maintain the open reading frame and to result in the removal of exactl…
Chi dice che i batteri fanno male? I CRISPR ed il loro potenziale genetico. In Le scienze naturali nella scuola
2019
L’immaginario collettivo non ha un’opinione buona e nemmeno benevola sui batteri. Sono spesso legati a concetti di mancanza di igiene, malattie ed a volte anche a situazioni più gravi financo la morte. È indubbio che alcuni generi di procarioti sono agenti patogeni di specifiche malattie infettive che, in passato più che oggi, hanno mietuto vittime nel genere umano. Ma che dire dei batteri lattici degli yogurt o della nostra flora batterica intestinale? C’è da aggiungere anche una lunga serie di organismi procarioti, non patogeni, che hanno, negli ultimi due secoli, costituito sistemi biologici idonei allo studio della biologia molecolare e della genetica molecolare. In definitiva è molto p…
The high-performance technology CRISPR/Cas9 improves knowledge and management of acute myeloid leukemia
2021
Knowledge on acute myeloid leukemia pathogenesis and treatment has progressed recently, but not enough to provide ideal management. Improving the prognosis of acute myeloid leukemia patients depends on advances in molecular biology for the detection of new therapeutic targets and the production of effective drugs. The CRISPR/Cas9 technology allows gene insertions and deletions and it is the first step in investigating the function of their encoded proteins. Thus, new experimental models have been developed and progress has been made in understanding protein metabolism, antitumor activity, leukemic cell maintenance, differentiation, growth, apoptosis, and self-renewal, the combined pathogene…
Murine liver organoids as a genetically flexible system to study liver cancer in vivo and in vitro.
2019
The rising incidence of cholangiocarcinoma (CCA) coupled with a low 5-year survival rate that remains below 10% delineates the urgent need for more effective treatment strategies. Although several recent studies provided detailed information on the genetic landscape of this fatal malignancy, versatile model systems to functionally dissect the immediate clinical relevance of the identified genetic alterations are still missing. To enhance our understanding of CCA pathophysiology and facilitate rapid functional annotation of putative CCA driver and tumor maintenance genes, we developed a tractable murine CCA model by combining the cyclization recombination (Cre)-lox system, RNA interference, …