RNA-guided retargeting of Sleeping Beauty transposition in human cells

An ideal tool for gene therapy would enable efficient gene integration at predetermined sites in the human genome. Here we demonstrate biased genome-wide integration of theSleeping Beauty (SB) transposon by combining it with components of the CRISPR/Cas9 system. We provide proof-of-concept that it is possible to influence the target site selection of SB by fusing it to a catalytically inactive Cas9 (dCas9) and by providing a single guide RNA (sgRNA) against the humanAlu retrotransposon. Enrichment of transposon integrations was dependent on the sgRNA, and occurred in an asymmetric pattern with a bias towards sites in a relatively narrow, 300-bp window downstream of the sgRNA targets. Our data indicate that the targeting mechanism specified by CRISPR/Cas9 forces integration into genomic regions that are otherwise poor targets for SB transposition. Future modifications of this technology may allow the development of methods for specific gene insertion for precision genetic engineering.
Source: eLife - Category: Biomedical Science Tags: Biochemistry and Chemical Biology Source Type: research

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Publication date: August 2020Source: Biomedicine &Pharmacotherapy, Volume 128Author(s): Hadi Esmaeili Gouvarchin Ghaleh, Masomeh Bolandian, Ruhollah Dorostkar, Ali Jafari, Mahdieh Farzaneh Pour
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Authors: Ghiasi B, Sefidbakht Y, Mozaffari-Jovin S, Gharehcheloo B, Mehrarya M, Khodadadi A, Rezaei M, Ranaei Siadat SO, Uskoković V Abstract The synthetic analogue to biogenic apatite, hydroxyapatite (HA) has a number of physicochemical properties that make it an attractive candidate for diagnosis, treatment of disease and augmentation of biological tissues. Here we describe some of the recent studies on HA, which may provide bases for a number of new medical applications. The content of this review is divided to different medical application modes utilizing HA, including tissue engineering, medical implants, con...
Source: Drug Development and Industrial Pharmacy - Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research
(Seattle Children's) Seattle Children's Research Institute, one of the top pediatric research institutions in the world, and global biotechnology leader CSL Behring announced a strategic alliance to develop stem cell gene therapies for primary immunodeficiency diseases.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Catalent, the leading global provider of advanced delivery technologies, development, and manufacturing solutions for drugs, biologics, cell and gene therapies, and consumer health products, today...(PRWeb June 02, 2020)Read the full story at https://www.prweb.com/releases/catalent_appoints_charles_lickfold_as_chief_information_officer/prweb17146590.htm
Source: PRWeb: Medical Pharmaceuticals - Category: Pharmaceuticals Source Type: news
BALA CYNWYD, Pa., June 1, 2020 -- (Healthcare Sales &Marketing Network) -- SwanBio Therapeutics, a gene therapy company developing leading-edge medicines to deliver dramatic clinical efficacy for the treatment of adrenomyeloneuropathy (AMN) and other neu... Biopharmaceuticals, Neurology, Personnel SwanBio Therapeutics, adeno-associated virus, adrenomyeloneuropathy
Source: HSMN NewsFeed - Category: Pharmaceuticals Source Type: news
An experimental gene therapy for hemophilia A from BioMarin Pharmaceutical Inc. — promising a one-shot fix for the genetic cause of the bleeding disorder — continues to hold patients' bleeds to less than one a year after four years. The results of the ongoing study are important as San Rafael-based BioMarin's (NASDAQ: BMRN) gene therapy, called Roctavian and known scienti fically as valoctogene roxaparvovec, nears an Aug. 21 decision date from the Food and Drug Administration. If approved, it…
Source: bizjournals.com Health Care:Biotechnology headlines - Category: Biotechnology Authors: Source Type: news
CONCLUSIONS: Based on the results of these clinical trials, the application of gene therapy in prostate cancer therapeutics can be satisfactorily established. PMID: 32473623 [PubMed - as supplied by publisher]
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - Category: Drugs & Pharmacology Tags: Endocr Metab Immune Disord Drug Targets Source Type: research
AbstractGene therapy has drawn great attention in the treatments of many diseases, especially for cardiovascular diseases. However, the development of gene carriers with low cytotoxicity and multitargeting function is still a challenge. Herein, the multitargeting REDV-G-TAT-GNLS peptide was conjugated to amphiphilic cationic copolymer poly( ε-caprolactone-co-3(S)-methyl-morpholine-2,5-dione)-g-polyethyleneimine (PCLMD-g-PEI) via a heterobifunctional orthopyridyl disulfide-poly(ethylene glycol)-N-hydroxysuccinimide (OPSS-PEG-NHS) linker to prepare PCLMD-g-PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop t...
Source: European Journal of Applied Physiology - Category: Physiology Source Type: research
This study aims to evaluate (1) the safety and (2) the e fficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min Walk Test distance, improvement of symptoms and assessment of quality of life.DiscussionThis study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formati...
Source: Trials - Category: Research Source Type: clinical trials
Cross-subtype neutralizing single domain antibodies against influenza present new opportunities for immunoprophylaxis and pandemic preparedness. Their simple modular structure and single open reading frame format are highly amenable to gene therapy-mediated delivery. We have previously described R1a-B6, an alpaca-derived single domain antibody (nanobody), that is capable of potent cross-subtype neutralization in vitro of H1N1, H5N1, H2N2, and H9N2 influenza viruses, through binding to a highly conserved epitope in the influenza hemagglutinin stem region. To evaluate the potential of R1a-B6 for immunoprophylaxis, we have re...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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