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Viral Vector Delivery of DREADDs for CNS Therapy
Ceri A Pickering1, Nicholas D Mazarakis1
1Division of Neuroscience, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.
Current Gene Therapy
|February 12, 2021
Summary
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable precise control of neural activity for neurological disorder research. This review evaluates viral vector delivery methods for DREADD gene therapy, assessing their potential and limitations.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are genetically engineered GPCRs activated by synthetic ligands.
- DREADDs allow for remote, reversible control of targeted cells in the central nervous system (CNS).
- They are valuable tools in neuroscience research and hold promise for neurological gene therapies.
Purpose of the Study:
- To review and evaluate viral vector delivery methods for DREADDs.
- To discuss the advantages and limitations of current DREADD delivery strategies.
- To identify improvements needed for DREADD gene therapy's translational potential.
Main Methods:
- Focus on adeno-associated virus (AAV)-based and lentivirus-based delivery systems.
- Analysis of cell-type specific promoters and pseudotyping for DREADD manipulation.
- Evaluation of existing literature on viral DREADD delivery strategies.
Main Results:
- DREADDs offer significant potential for neurological disorder gene therapy.
- Viral vector delivery methods, including AAV and lentivirus, have distinct pros and cons.
- Cell-type specific promoters and pseudotyping are key for targeted DREADD expression.
Conclusions:
- Optimizing viral DREADD delivery is crucial for advancing gene therapy for neurological disorders.
- Further research into improving delivery methods will expand the translational potential of DREADDs.
- DREADDs represent a promising chemogenetic approach for future therapeutic interventions.
