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 TALEN Mediated Gene Targeting for CF Gene Therapy

2018 ◽  
Author(s):  
Emily Xia ◽  
Yiqian Zhang ◽  
Huibi Cao ◽  
Jun Li ◽  
Rongqi Duan ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Editing ◽  
Airway Epithelial Cells ◽  
In Vivo Studies ◽  
Lacz Reporter ◽  
Gene Correction ◽  
Transcription Activator ◽  
Stringent Requirement

Cystic Fibrosis (CF) is an inherited monogenic disorder, amenable to gene based therapies. Because CF lung disease is currently the major cause of mortality and morbidity, and lung airway is readily accessible to gene delivery, the major CF gene therapy effort at present is directed to the lung. Although airway epithelial cells are renewed slowly, permanent gene correction through gene editing or targeting in airway stem cells is needed to perpetuate the therapeutic effect. Transcription activator-like effector nuclease (TALEN) has been utilized widely for a variety of gene editing applications. The stringent requirement for nuclease binding target sites allows for gene editing with precision. In this study, we engineered helper-dependent adenoviral (HD-Ad) vectors to deliver a pair of TALENs together with donor DNA targeting the human AAVS1 locus. With homology arms of 4 kb in length, we demonstrated precise insertion of either a LacZ reporter gene or a human CFTR minigene into the target site. Using the LacZ reporter, we determined the efficiency of gene integration to be about 5%. In the CFTR vector transduced cells, we have detected both CFTR mRNA and protein expression by qPCR and Wetern analysis, respectively. We have also confirmed CFTR function correction by flurometric Image Plate Reader (FLIPR) and iodide efflux assays. Taking together, these findings suggest a new direction for future in vitro and in vivo studies in CF gene editing.

scholarly journals Gene Therapy for Cardiovascular Disease

2003 ◽  
Vol 2003 (2) ◽  
pp. 138-148 ◽  
Author(s):  
Kate L. Dishart ◽  
Lorraine M. Work ◽  
Laura Denby ◽  
Andrew H. Baker
Keyword(s):  
Cardiovascular Disease ◽  
Gene Therapy ◽  
Drug Therapy ◽  
Cardiovascular Diseases ◽  
Gene Transfer ◽  
Animal Models ◽  
Pharmacological Treatments ◽  
Therapy Strategies ◽  
Vascular Gene Transfer

The last decade has seen substantial advances in the development of gene therapy strategies and vector technology for the treatment of a diverse number of diseases, with a view to translating the successes observed in animal models into the clinic. Perhaps the overwhelming drive for the increase in vascular gene transfer studies is the current lack of successful long-term pharmacological treatments for complex cardiovascular diseases. The increase in cardiovascular disease to epidemic proportions has also led many to conclude that drug therapy may have reached a plateau in its efficacy and that gene therapy may represent a realistic solution to a long-term problem. Here, we discuss gene delivery approaches and target diseases.

A critical view of CRISPR applications in Human Genetics

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
José Luis Ramírez Ochoa
Keyword(s):  
Gene Therapy ◽  
Human Health ◽  
Gene Editing ◽  
Human Genetics ◽  
Comprehensive Review ◽  
New Era ◽  
Critical View ◽  
New Horizons ◽  
Ethical Concerns ◽  
Short Period

Gene therapy entered a new era with CRISPR gene-editing technology. In a short period of eight years, CRISPR revolutionized how we handle genes by simplifying and democratizing the tools for gene editing. CRISPR applications in human health are exponentially growing and opening new horizons for otherwise difficult diseases to treat. Nonetheless, the versatility, easiness, and wide use of this technology in humans are creating new bioethical challenges. Here, aiming to non-experts, students, and researchers, I briefly review some relevant aspects of CRISPR history and evolution, as well as some ethical concerns related to its use in humans. To pretend to do a comprehensive review on CRISPR is a futile task since the speed of its evolution would render it obsolete by the time of its publication.

scholarly journals Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Hongyi Li ◽  
Yang Yang ◽  
Weiqi Hong ◽  
Mengyuan Huang ◽  
Min Wu ◽  
...  
Keyword(s):  
Animal Models ◽  
Genome Editing ◽  
Gene Editing ◽  
Basic Research ◽  
Human Diseases ◽  
Eukaryotic Cells ◽  
Zinc Finger Nucleases ◽  
Transcription Activator ◽  
Major Genome ◽  
Almost All

AbstractBased on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)–Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.

scholarly journals Prediction of Cardiovascular Diseases based on Machine Learning

2021 ◽  
Vol 1 (1) ◽  
pp. 30-35
Author(s):  
Weicheng Sun ◽  
Ping Zhang ◽  
Zilin Wang ◽  
Dongxu Li
Keyword(s):  
Machine Learning ◽  
Cardiovascular Disease ◽  
Support Vector Machine ◽  
Cardiovascular Diseases ◽  
Rapid Development ◽  
Support Vector ◽  
Functional Dependencies ◽  
Computer Methods ◽  
Mechanical Methods ◽  
Logical Regression

With the rapid development of artificial intelligence, it is very important to find the pattern of the data from the observed data and the functional dependency relationship between the data. By finding the existing functional dependencies, we can classify and predict them. At present, cardiovascular disease has become a major disease harmful to human health. As a disease with high mortality, the prediction problem of cardiovascular disease is becoming more and more urgent. However, some computer methods are mainly used for disease detection rather than prediction. If the computer method can be used to predict cardiovascular disease in advance and treat it as early as possible, then the consequences of the disease can be reduced to a certain extent. Diseases can be predicted by mechanical methods. Support vector machine (SVM) has strict mathematical theory support, and can deal with nonlinear classification after using kernel techniques. Therefore, support vector machine can be used to predict cardiovascular disease. On the other hand, we also use logical regression and random forest to predict cardiovascular disease. This paper mainly uses the method of machine learning to predict whether the population is sick or not. First of all, we preprocess the obtained data to improve the quality of the data, and then use svm and logical regression to predict, so as to provide reference for the prevention and treatment of cardiovascular diseases.

scholarly journals Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

2020 ◽  
Vol 9 (8) ◽  
pp. 2577 ◽  
Author(s):  
Lucía Bañuls ◽  
Daniel Pellicer ◽  
Silvia Castillo ◽  
María Mercedes Navarro-García ◽  
María Magallón ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Respiratory Diseases ◽  
Viral Vectors ◽  
Gene Editing ◽  
Alternative Therapy ◽  
Transcription Activator ◽  
Gene Therapy Approach ◽  
Gene Therapy Application ◽  
Alpha 1 Antitrypsin Deficiency

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical trials targeting CF and AATD, especially using adeno-associated viral vectors, resulting in a good safety profile but with low efficacy in protein expression. Other strategies, such as non-viral vectors and more recently gene editing tools, have also been used to address these diseases in pre-clinical studies. The first gene therapy approach in PCD was in 2009 when a lentiviral transduction was performed to restore gene expression in vitro; since then, transcription activator-like effector nucleases (TALEN) technology has also been applied in primary cell culture. Gene therapy is an encouraging alternative treatment for these respiratory diseases; however, more research is needed to ensure treatment safety and efficacy.

scholarly journals TALEN-Mediated Gene Targeting for Cystic Fibrosis-Gene Therapy

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 39 ◽  
Author(s):  
Emily Xia ◽  
Yiqian Zhang ◽  
Huibi Cao ◽  
Jun Li ◽  
Rongqi Duan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Gene Editing ◽  
Airway Epithelial Cells ◽  
In Vivo Studies ◽  
Cystic Fibrosis Gene ◽  
Lacz Reporter ◽  
Gene Correction ◽  
Transcription Activator ◽  
Stringent Requirement

Cystic fibrosis (CF) is an inherited monogenic disorder, amenable to gene-based therapies. Because CF lung disease is currently the major cause of mortality and morbidity, and the lung airway is readily accessible to gene delivery, the major CF gene therapy effort at present is directed to the lung. Although airway epithelial cells are renewed slowly, permanent gene correction through gene editing or targeting in airway stem cells is needed to perpetuate the therapeutic effect. Transcription activator-like effector nuclease (TALEN) has been utilized widely for a variety of gene editing applications. The stringent requirement for nuclease binding target sites allows for gene editing with precision. In this study, we engineered helper-dependent adenoviral (HD-Ad) vectors to deliver a pair of TALENs together with donor DNA targeting the human AAVS1 locus. With homology arms of 4 kb in length, we demonstrated precise insertion of either a LacZ reporter gene or a human cystic fibrosis transmembrane conductance regulator (CFTR) minigene (cDNA) into the target site. Using the LacZ reporter, we determined the efficiency of gene integration to be about 5%. In the CFTR vector transduced cells, we were able to detect CFTR mRNA expression using qPCR and function correction using fluorometric image plate reader (FLIPR) and iodide efflux assays. Taken together, these findings suggest a new direction for future in vitro and in vivo studies in CF gene editing.

Gene therapy for cardiovascular diseases in China: basic research

Gene Therapy ◽  
2020 ◽  
Vol 27 (7-8) ◽  
pp. 360-369 ◽  
Author(s):  
Jiali Deng ◽  
Mengying Guo ◽  
Guoping Li ◽  
Junjie Xiao
Keyword(s):  
Gene Therapy ◽  
Cardiovascular Diseases ◽  
Basic Research

NT-PROBNP AND THE CUT-OFF VALUE IN CARDIOVASCULAR DISEASES

2011 ◽  
pp. 5-12
Author(s):  
Anh Tien Hoang ◽  
Van Minh Huynh ◽  
Khanh Hoang ◽  
Huu Dang Tran ◽  
Viet An Tran
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Pilot Study ◽  
Cardiovascular Diseases ◽  
Clinical Application ◽  
European Society ◽  
The Other ◽  
Cardiac Marker ◽  
Cardiac Biomarker ◽  
European Society Of Cardiology

NT-ProBNP is a high value cardiac biomarker and widely applies in many cardiovascular diseases. The evaluation of concentration of NT-ProBNP needs the concern about age, gender, obesity and especially we need each cut-off point for each cause of cardiovascular disease in evaluation and clinical application. Because NT-ProBNP is a new cardiac marker and has been researched in 5 recent years, the cut-off of NT-ProBNP is still being studied for the clinical application in cardiovascular diseases. Only the cut-off of NT-ProBNP in diagnosis heart failure was guided by European Society of Cardiology. The meaning of introduce cut-off value of value plays an role as pilot study for the other relate study and brings the NT-ProBNP closely approach to clinical application.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

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