scholarly journals Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application

2017 ◽  
Vol 56 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Deepthi Alapati ◽  
Edward E. Morrisey
Keyword(s):  
Lung Disease ◽  
Gene Editing ◽  
Basic Research ◽  
Therapeutic Application

scholarly journals In utero gene editing for monogenic lung disease

2019 ◽  
Vol 11 (488) ◽  
pp. eaav8375 ◽  
Author(s):  
Deepthi Alapati ◽  
William J. Zacharias ◽  
Heather A. Hartman ◽  
Avery C. Rossidis ◽  
John D. Stratigis ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Gene Editing ◽  
In Utero ◽  
Lung Damage ◽  
Secretory Cells ◽  
Specific Gene ◽  
Alveolar Type ◽  
Diffuse Parenchymal Lung Disease ◽  
Parenchymal Lung

Monogenic lung diseases that are caused by mutations in surfactant genes of the pulmonary epithelium are marked by perinatal lethal respiratory failure or chronic diffuse parenchymal lung disease with few therapeutic options. Using a CRISPR fluorescent reporter system, we demonstrate that precisely timed in utero intra-amniotic delivery of CRISPR-Cas9 gene editing reagents during fetal development results in targeted and specific gene editing in fetal lungs. Pulmonary epithelial cells are predominantly targeted in this approach, with alveolar type 1, alveolar type 2, and airway secretory cells exhibiting high and persistent gene editing. We then used this in utero technique to evaluate a therapeutic approach to reduce the severity of the lethal interstitial lung disease observed in a mouse model of the human SFTPCI73T mutation. Embryonic expression of SftpcI73T alleles is characterized by severe diffuse parenchymal lung damage and rapid demise of mutant mice at birth. After in utero CRISPR-Cas9–mediated inactivation of the mutant SftpcI73T gene, fetuses and postnatal mice showed improved lung morphology and increased survival. These proof-of-concept studies demonstrate that in utero gene editing is a promising approach for treatment and rescue of monogenic lung diseases that are lethal at birth.

Advances in therapeutic application of CRISPR-Cas9

2019 ◽  
Vol 19 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Jinyu Sun ◽  
Jianchu Wang ◽  
Donghui Zheng ◽  
Xiaorong Hu
Keyword(s):  
Gene Therapy ◽  
Genome Editing ◽  
Malignant Tumor ◽  
Gene Editing ◽  
Genome Engineering ◽  
Therapeutic Application ◽  
Adaptive Immune ◽  
Efficient Gene

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) is one of the most versatile and efficient gene editing technologies, which is derived from adaptive immune strategies for bacteria and archaea. With the remarkable development of programmable nuclease-based genome engineering these years, CRISPR-Cas9 system has developed quickly in recent 5 years and has been widely applied in countless areas, including genome editing, gene function investigation and gene therapy both in vitro and in vivo. In this paper, we briefly introduce the mechanisms of CRISPR-Cas9 tool in genome editing. More importantly, we review the recent therapeutic application of CRISPR-Cas9 in various diseases, including hematologic diseases, infectious diseases and malignant tumor. Finally, we discuss the current challenges and consider thoughtfully what advances are required in order to further develop the therapeutic application of CRISPR-Cas9 in the future.

scholarly journals Gene editing in dermatology: Harnessing CRISPR for the treatment of cutaneous disease

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 281
Author(s):  
Catherine Baker ◽  
Matthew S. Hayden
Keyword(s):  
Human Genome ◽  
Genome Editing ◽  
Gene Editing ◽  
Human Diseases ◽  
Therapeutic Application ◽  
Cutaneous Disease ◽  
Crispr System ◽  
Novel Approaches

The discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has revolutionized gene editing research. Through the repurposing of programmable RNA-guided CRISPR-associated (Cas) nucleases, CRISPR-based genome editing systems allow for the precise modification of specific sites in the human genome and inspire novel approaches for the study and treatment of inherited and acquired human diseases. Here, we review how CRISPR technologies have stimulated key advances in dermatologic research.  We discuss the role of CRISPR in genome editing for cutaneous disease and highlight studies on the use of CRISPR-Cas technologies for genodermatoses, cutaneous viruses and bacteria, and melanoma. Additionally, we examine key limitations of current CRISPR technologies, including the challenges these limitations pose for the widespread therapeutic application of CRISPR-based therapeutics.

scholarly journals Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Huimin Zhang ◽  
Chunhong Qin ◽  
Changming An ◽  
Xiwang Zheng ◽  
Shuxin Wen ◽  
...  
Keyword(s):  
Cancer Research ◽  
Gene Editing ◽  
Basic Research ◽  
Genomic Locus ◽  
Future Directions ◽  
Genomic Changes ◽  
Diagnosis And Therapy ◽  
Oncology Research ◽  
Potential Applications ◽  
A Site

AbstractThe 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of tumorigenesis and development. In recent years, the CRISPR/Cas9 system has been increasingly used in cancer research and treatment and remarkable results have been achieved. In this review, we introduced the mechanism and development of the CRISPR/Cas9-based gene editing system. Furthermore, we summarized current applications of this technique for basic research, diagnosis and therapy of cancer. Moreover, the potential applications of CRISPR/Cas9 in new emerging hotspots of oncology research were discussed, and the challenges and future directions were highlighted.

scholarly journals Improved Cas9 activity by specific modifications of the tracrRNA

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tristan Scott ◽  
Ryan Urak ◽  
Citradewi Soemardy ◽  
Kevin V. Morris
Keyword(s):  
T Cells ◽  
Streptococcus Pyogenes ◽  
Gene Editing ◽  
Basic Research ◽  
Clinical Applications ◽  
Receptor Expression ◽  
Guide Rna ◽  
Surface Receptor ◽  
Endogenous Genes ◽  
Mediated Reduction

Abstract CRISPR/Cas is a transformative gene editing tool, that offers a simple and effective way to target a catalytic Cas9, the most widely used is derived from Streptococcus pyogenes (SpCas9), with a complementary small guide RNA (sgRNA) to inactivate endogenous genes resulting from insertions and deletions (indels). CRISPR/Cas9 has been rapidly applied to basic research as well as expanded for potential clinical applications. Utilization of spCas9 as an ribonuclearprotein complex (RNP) is considered the most safe and effective method to apply Cas9 technology, and the efficacy of this system is critically dependent on the ability of Cas9 to generate high levels of indels. We find here that novel sequence changes to the tracrRNA significantly improves Cas9 activity when delivered as an RNP. We demonstrate that a dual-guide RNA (dgRNA) with a modified tracrRNA can improve reporter knockdown and indel formation at several targets within the long terminal repeat (LTR) of HIV. Furthermore, the sequence-modified tracrRNAs improved Cas9-mediated reduction of CCR5 surface receptor expression in cell lines, which correlated with higher levels of indel formation. It was demonstrated that a Cas9 RNP with a sequence modified tracrRNA enhanced indel formation at the CCR5 target site in primary CD4+ T-cells. Finally, we show improved activity at two additional targets within the HBB locus and the BCL11A GATA site. Overall, the data presented here suggests that novel facile tracrRNA sequence changes could potentially be integrated with current dgRNA technology, and open up the possibility for the development of sequence modified tracrRNAs to improve Cas9 RNP activity.

scholarly journals Gene editing in Brassica napus for basic research and trait development

2021 ◽  
Author(s):  
Greg F. W. Gocal
Keyword(s):  
Brassica Napus ◽  
Gene Editing ◽  
Basic Research ◽  
Oilseed Crop ◽  
Delivery Methods ◽  
Grain Composition ◽  
History Of ◽  
Pod Shatter ◽  
New Alleles ◽  
Trait Development

AbstractThe genome of Brassica napus L. is the result of several polyploidization events that occurred during the history of B. napus. Due to its relatively short domestication history, diversity is relatively limited. An increasing number of loci in this crop’s genome have been gene-edited using various technologies and reagent delivery methods for basic research as well as for trait development. New alleles have been developed as edits in single, 2, 4, or more homologous loci in this important oilseed crop. This comprehensive review will summarize new alleles that have been developed as they relate to weed control, flowering, self-incompatibility, plant hormone biology, disease resistance, grain composition, and pod shatter reduction. These new alleles have significantly augmented our understanding of both plant growth and development for basic research as well as for their potential commercial impacts.

scholarly journals Gene Therapy for Cardiovascular Disease: Basic Research and Clinical Prospects

2021 ◽  
Vol 8 ◽  
Author(s):  
Genmao Cao ◽  
Xuezhen Xuan ◽  
Ruijing Zhang ◽  
Jie Hu ◽  
Honglin Dong
Keyword(s):  
Cardiovascular Disease ◽  
Gene Therapy ◽  
Cardiovascular Diseases ◽  
Gene Editing ◽  
Rapid Development ◽  
Basic Research ◽  
Early Years ◽  
Transcription Activator ◽  
Term Survival ◽  
Ethical Concerns

In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein–nucleic acids complexes—CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.

scholarly journals CRISPR with independent transgenes is a safe and robust alternative to autonomous gene drives in basic research

2015 ◽  
Author(s):  
Fillip Port ◽  
Nadine Muschalik ◽  
Simon L Bullock
Keyword(s):  
Gene Editing ◽  
Genome Engineering ◽  
High Efficiency ◽  
Basic Research ◽  
Evidence Based ◽  
Gene Drive ◽  
Highly Active ◽  
Genome Modification ◽  
Target Sites ◽  
Gene Drives

CRISPR/Cas technology allows rapid, site-specific genome modification in a wide variety of organisms. CRISPR components produced by integrated transgenes have been shown to mutagenise some genomic target sites in Drosophila melanogaster with high efficiency, but whether this is a general feature of this system remains unknown. Here, we systematically evaluate available CRISPR/Cas reagents and experimental designs in Drosophila. Our findings allow evidence-based choices of Cas9 sources and strategies for generating knock-in alleles. We perform gene editing at a large number of target sites using a highly active Cas9 line and a collection of transgenic gRNA strains. The vast majority of target sites can be mutated with remarkable efficiency using these tools. We contrast our method to recently developed autonomous gene drive technology for genome engineering (Gantz & Bier, 2015) and conclude that optimised CRISPR with independent transgenes is as efficient, more versatile and does not represent a biosafety risk.

Neurotoxins from invertebrates as anticonvulsants: From basic research to therapeutic application

2007 ◽  
Vol 114 (2) ◽  
pp. 171-183 ◽  
Author(s):  
Márcia Renata Mortari ◽  
Alexandra Olimpio Siqueira Cunha ◽  
Luzitano Brandão Ferreira ◽  
Wagner Ferreira dos Santos
Keyword(s):  
Basic Research ◽  
Therapeutic Application
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