scholarly journals Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond

2017 ◽  
Vol 28 (4) ◽  
pp. 361-372 ◽  
Author(s):  
Paul N. Valdmanis ◽  
Mark A. Kay
Keyword(s):  
Gene Therapy ◽  
Gene Editing ◽  
Raav Gene Therapy

scholarly journals Latest Advances of Virology Research Using CRISPR/Cas9-Based Gene-Editing Technology and Its Application to Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 779
Author(s):  
Man Teng ◽  
Yongxiu Yao ◽  
Venugopal Nair ◽  
Jun Luo
Keyword(s):  
Biological Sciences ◽  
Gene Therapy ◽  
Genetic Engineering ◽  
Gene Function ◽  
Viral Genome ◽  
Gene Editing ◽  
Vaccine Development ◽  
Future Prospects ◽  
Dna Viruses ◽  
Viral Genomes

In recent years, the CRISPR/Cas9-based gene-editing techniques have been well developed and applied widely in several aspects of research in the biological sciences, in many species, including humans, animals, plants, and even in viruses. Modification of the viral genome is crucial for revealing gene function, virus pathogenesis, gene therapy, genetic engineering, and vaccine development. Herein, we have provided a brief review of the different technologies for the modification of the viral genomes. Particularly, we have focused on the recently developed CRISPR/Cas9-based gene-editing system, detailing its origin, functional principles, and touching on its latest achievements in virology research and applications in vaccine development, especially in large DNA viruses of humans and animals. Future prospects of CRISPR/Cas9-based gene-editing technology in virology research, including the potential shortcomings, are also discussed.

Potential HIV gene therapy strategies

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Cord Blood ◽  
Gene Editing ◽  
Mortality Risks ◽  
Recent Advances ◽  
Whole Exome ◽  
Localization Signal ◽  
Cord Blood Cells ◽  
The Cost ◽  
Therapy Strategies

The CCR5 null genotype generation has been a main focus in the HIV gene therapy industry. The presence of the X4 tropic virus, mobilization of HSPCs, the quality of the cells for manipulation, and gene editing efficiency appear to be the main obstacles in translating this technique. Unintended off-target cleavage is a key problem in CRISPR/Cas9 editing. With the development of small molecule expansion methods for cord blood HSPC, it would be advantageous to modify CCR5 in cord blood cells and expand them for transplantation. The generation of engraftable HSPCS from iPSCs would be an ideal technique for HSCC gene therapy.The haplotype-characterized iPSC would be the donor for many patients, and it could be a commercially available product. The 32 C CR5 homozygous people had no elevated mortality risks according to whole-exome sequencing and whole-genome genotyping, according to CCR 5 positive people, and had no higher mortality risks compared to those who were HIV positive. Recent advances in gene editing, such as non-viral delivery of Cas9 ribonucleoproteins, incorporation of a 3X-nuclear localization signal into spCas9, and use of HiFi Cas9 with chemically modified sgRNAs, can be combined with recent advances in transplantation. Infusing modest doses of gene modified primitive HSPC fractions indicated by CD34 + CD90 + CD45RA-, which can engraft better, is another option for lowering the cost of gene therapy.

scholarly journals GENE THERAPY FOR HAEMOPHILIA

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
A Asghar ◽  
Z Asjad ◽  
H Tahir ◽  
Z Maheen ◽  
S Hanif
Keyword(s):  
Gene Therapy ◽  
Gene Editing ◽  
Genetic Disorders ◽  
Coagulation Factor ◽  
Retroviral Vectors ◽  
Adeno Associated Virus ◽  
General Application ◽  
Blood Disorder ◽  
Statistical Consideration ◽  
History Of

The blood disorder, Hemophilia, has its roots embedded deep into the history of genetic disorders. The European royal family is one of the most prominent families to be affected by this disease thus, dubbing it 'the royal disease'. The types of Hemophilia are divided into two based on the type of coagulation factor mutation found in the patient. For treating haemophilia, gene therapy is done by using different vectors such as lentiviral and retroviral vectors but due to the production of limited expression different adeno associated virus (AAV) strains are used. Some engineerly modified vectors are currently used to get the best possible results. The clinical trials prove the efficacy of these vectors so through their obtained statistical consideration, patient experience and population study once can design vaccines and drugs for haemophilia patients but also due to pre-existing Nabs and pre-existing HCV or HBV infection, the general application of AAV gene therapy is currently limited. The possibility of gene editing for the repair of the mutation is on the horizon.

scholarly journals Design of time-delayed safety switches for CRISPR gene therapy

2021 ◽  
Author(s):  
Dashan Sun
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Time Delay ◽  
Cell Lines ◽  
Gene Editing ◽  
Drug Accumulation ◽  
Work Time ◽  
Crispr System ◽  
Efficient Gene ◽  
Target Effect

CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. In our work, time-delayed safety switches are designed based on either artificial ultrasensitivity transmission module or intrinsic time delay in biomolecular activities. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.

Hematopoietic stem cell gene therapy: The optimal use of lentivirus and gene editing approaches

Blood Reviews ◽  
2020 ◽  
Vol 40 ◽  
pp. 100641 ◽  
Author(s):  
Andrés Lamsfus-Calle ◽  
Alberto Daniel-Moreno ◽  
Guillermo Ureña-Bailén ◽  
Janani Raju ◽  
Justin S. Antony ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Gene Editing ◽  
Hematopoietic Stem ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Stem Cell Gene Therapy

Gene Therapy and Gene Editing for Myotonic Dystrophy

2019 ◽  
pp. 525-548
Author(s):  
Marinee Chuah ◽  
Yoke Chin Chai ◽  
Sumitava Dastidar ◽  
Thierry VandenDriessche
Keyword(s):  
Gene Therapy ◽  
Myotonic Dystrophy ◽  
Gene Editing

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 Effects of hypothalamic leptin gene therapy on osteopetrosis in leptin-deficient mice

2018 ◽  
Vol 236 (2) ◽  
pp. 57-68 ◽  
Author(s):  
Kenneth A Philbrick ◽  
Stephen A Martin ◽  
Amy R Colagiovanni ◽  
Adam J Branscum ◽  
Russell T Turner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Turnover ◽  
Fluorescent Protein ◽  
Cellular Level ◽  
Cartilage Matrix ◽  
Adeno Associated Virus ◽  
Green Fluorescent ◽  
Old Mice ◽  
Deficient Mice ◽  
Raav Gene Therapy

Impaired resorption of cartilage matrix deposited during endochondral ossification is a defining feature of juvenile osteopetrosis. Growing, leptin-deficient ob/ob mice exhibit a mild form of osteopetrosis. However, the extent to which the disease is (1) self-limiting and (2) reversible by leptin treatment is unknown. We addressed the first question by performing histomorphometric analysis of femurs in rapidly growing (2-month-old), slowly growing (4-month-old) and skeletally mature (6-month-old) wild-type (WT) and ob/ob male mice. Absent by 6 months of age in WT mice, cartilage matrix persisted to varying extents in distal femur epiphysis, metaphysis and diaphysis in ob/ob mice, suggesting that the osteopetrotic phenotype is not entirely self-limiting. To address the second question, we employed hypothalamic recombinant adeno-associated virus (rAAV) gene therapy to restore leptin signaling in ob/ob mice. Two-month-old mice were randomized to one of the three groups: (1) untreated control, (2) rAAV-Leptin or (3) control vector rAAV-green fluorescent protein and vectors injected intracerebroventricularly. Seven months later, rAAV-leptin-treated mice exhibited no cartilage in the metaphysis and greatly reduced cartilage in the epiphysis and diaphysis. At the cellular level, the reduction in cartilage was associated with increased bone turnover. These findings (1) support the concept that leptin is important for normal replacement of cartilage by bone, and (2) demonstrate that osteopetrosis in ob/ob mice is bone-compartment-specific and reversible by leptin at skeletal sites capable of undergoing robust bone turnover.

scholarly journals CRISPR/Cas-based Diagnostics and Gene Therapy

2021 ◽  
Author(s):  
Qiu Meiyu ◽  
Li Pei
Keyword(s):  
Gene Therapy ◽  
Gene Editing ◽  
Ex Vivo ◽  
Point Of Care ◽  
Cost Effective ◽  
Blood Disorders ◽  
Initial Stage ◽  
Cas Gene ◽  
Cas Proteins

Clustered regularly interspaced short palindromic repeats (CRISPR) technology, an easy, rapid, cost-effective, and precise gene-editing technique, has revolutionized diagnostics and gene therapy. Fast and accurate diagnosis of diseases is essential for point-of-care-testing (POCT) and specialized medical institutes. The CRISPR-associated (Cas) proteins system shed light on the new diagnostics methods at point-of-care (POC) owning to its advantages. In addition, CRISPR/Cas-based gene-editing technology has led to various breakthroughs in gene therapy. It has been employed in clinical trials for a variety of untreatable diseases, including cancer, blood disorders, and other syndromes. Currently, the clinical application of CRISPR/Cas has been mainly focused on ex vivo therapies. Recently, tremendous efforts have been made in the development of ex vivo gene therapy based on CRISPR-Cas9. Despite these efforts, in vivo CRISPR/Cas gene therapy is only in its initial stage. Here, we review the milestones of CRISPR/Cas technologies that advanced the field of diagnostics and gene therapy. We also highlight the recent advances of diagnostics and gene therapy based on CRISPR/Cas technology. In the last section, we discuss the strength and significant challenges of the CRISPR/Cas technology for its future clinical usage in diagnosis and gene therapy.

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