Viral Vector Delivery of DREADDs for CNS Therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Ceri A. Pickering ◽  
Nicholas D. Mazarakis
Keyword(s):  
Gene Therapy ◽  
Viral Vector ◽  
Designer Drugs ◽  
Target Cells ◽  
Delivery Methods ◽  
Therapy Strategy ◽  
Synthetic Ligand ◽  
The Central Nervous System ◽  
Gene Therapy Strategy ◽  
Vector Delivery

: Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are genetically modified G-protein-coupled receptors (GPCRs), which can be activated by a synthetic ligand that is otherwise inert at endogenous receptors. DREADDs can be expressed in cells in the central nervous system (CNS) and subsequently offer the opportunity for remote and reversible silencing or activation of the target cells when the synthetic ligand is systemically administered. In neuroscience, DREADDs have thus far shown to be useful tools for several areas of research. Furthermore, they offer considerable potential for use as a gene therapy strategy for neurological disorders. However, in order to design a DREADD-based gene therapy, it is necessary to first evaluate the viral vector delivery methods utilised to deliver these chemogenetic tools in the literature. This review evaluates each of the prominent strategies currently utilised for DREADD delivery, discussing their respective advantages and limitations. It focuses on Adeno-Associated Virus (AAV)- and lentivirus-based systems, and the manipulation of these through cell-type specific promoters and pseudotyping. Furthermore, we address how virally mediated DREADD delivery could be improved in order to make it a viable gene therapy strategy and thus expand its translational potential.

scholarly journals Gene therapy strategy of glomerulosclerosis.

Ensho ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 265-269
Author(s):  
Yasufumi Kaneda ◽  
Yoshitaka Isaka ◽  
Enyu Imai
Keyword(s):  
Gene Therapy ◽  
Therapy Strategy ◽  
Gene Therapy Strategy

scholarly journals Peritoneal Dialysis in the 21st Century: The Potential of Gene Therapy

2002 ◽  
Vol 13 (suppl 1) ◽  
pp. S117-S124
Author(s):  
Catherine M. Hoff ◽  
Ty R. Shockley
Keyword(s):  
Gene Therapy ◽  
Peritoneal Dialysis ◽  
Genetic Engineering ◽  
Genetic Manipulation ◽  
Membrane Damage ◽  
Peritoneal Membrane ◽  
Functional Changes ◽  
Therapy Strategy ◽  
Transfer Strategies ◽  
Gene Therapy Strategy

ABSTRACT. One of the greatest biotechnologic advances of the last 25 yr is genetic engineering—the ability to identify and isolate individual genes and transfer genetic elements between cells. Genetic engineering forms the basis of a unique biotechnology platform called gene therapy: an approach to treating disease through genetic manipulation. It is becoming clear that during peritoneal dialysis, the peritoneal membrane undergoes various structural and functional changes that compromise the dialyzing efficiency of the membrane and eventually lead to membrane failure. A gene therapy strategy based on genetic modification of the peritoneal membrane could improve the practice of peritoneal dialysis through the production of proteins that would be of therapeutic value in preventing membrane damage and preserving its dialyzing capacity. The peritoneal membrane can be genetically modified by either ex vivo or in vivo gene transfer strategies with a variety of potentially therapeutic genes, including those for anti-inflammatory cytokines, fibrinolytic factors, and antifibrotic molecules. These genes could be administered either on an acute basis, such as in response to peritonitis, or on an intermittent basis to maintain physiologic homeostasis and perhaps to prevent the adverse changes in the membrane that occur over time. The anticipated effect of a gene therapy strategy could be measured in maintenance of desired transport characteristics and in patients being able to remain on the therapy for longer periods of time without the negative outcomes. In summary, the use of a gene therapy strategy to enhance peritoneal dialysis is an innovative and exciting concept with the potential to provide new treatment platforms for patients with end-stage renal disease.

scholarly journals France plans national gene therapy strategy

Nature ◽  
1994 ◽  
Vol 372 (6505) ◽  
pp. 397-397
Author(s):  
Declan Butler
Keyword(s):  
Gene Therapy ◽  
Therapy Strategy ◽  
Gene Therapy Strategy

scholarly journals Data-driven evolution of neurosurgical gene therapy delivery in Parkinson’s disease

2020 ◽  
Vol 91 (11) ◽  
pp. 1210-1218 ◽  
Author(s):  
R Mark Richardson ◽  
Krystof S Bankiewicz ◽  
Chadwick W Christine ◽  
Amber D Van Laar ◽  
Robert E Gross ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Viral Vector ◽  
Data Driven ◽  
Surgical Approaches ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Virus Serotype ◽  
Vector Delivery

Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson’s disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. These challenges have recently been addressed during the evolution of novel techniques for vector delivery that include the use of intraoperative MRI. The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery.

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