Source 1review2015Neuroscience
Toolkit/designer receptors exclusively activated by designer drug
designer receptors exclusively activated by designer drug
Also known as: designer receptors exclusively activated by designer drugs, DREADD, Gq-coupled human M3 muscarinic receptor, hM3Dq
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Designer receptors exclusively activated by designer drug (DREADDs) are engineered G protein-coupled receptors used as a chemogenetic or pharmacogenetic system. They enable selective remote control of neuronal activity through activation by otherwise inert drug-like small molecules.
Usefulness & Problems
Why this is useful
This tool is useful for selective remote control of neuronal activity in studies of nervous system function. The cited review places chemogenetic tools such as DREADDs within a broader toolbox that has enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
Source:
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
Source:
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Source:
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Problem solved
DREADDs address the problem of modulating neuronal activity selectively without relying on endogenous receptor activation, by using engineered receptors responsive to otherwise inert drug-like small molecules. This provides a pharmacogenetic route for remote control of targeted cells.
Source:
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Techniques
Computational DesignTarget processes
recombinationInput: Light
Implementation Constraints
Implementation requires expression of an engineered G protein-coupled receptor and administration of an otherwise inert drug-like small molecule to activate it. The supplied evidence does not describe construct architecture, delivery method, host organism, or dosing parameters.
The supplied evidence does not specify receptor variants, ligand identities, signaling bias, temporal resolution, or quantitative performance. It also does not provide direct validation details beyond general use for neuronal activity control.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successMouseapplication demomousestriatum
behavioral rescue
Inferred from claim c3 during normalization. Enhancing striatopallidal medium spiny neuron activity with hM3Dq DREADD rescued repetitive grooming behavior in Shank3B mutant mice. Derived from claim c3. Quoted text: the repetitive grooming behavior was rescued by selectively enhancing the striatopallidal MSN activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq)
Source:
Supporting Sources
Source 2primary paper2017Harvard Review of Psychiatry
Source 3primary paper2016Scientific Reports
Source 4review2017American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Source 5primary paper2017Journal of Clinical Investigation
Ranked Claims
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
Enhancing striatopallidal medium spiny neuron activity with hM3Dq DREADD rescued repetitive grooming behavior in Shank3B mutant mice.
the repetitive grooming behavior was rescued by selectively enhancing the striatopallidal MSN activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq)
Genetically modified viral vectors broaden the ability to express genes of interest and support inducible manipulations in neural systems.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Bioengineered light-sensitive ion channels including channelrhodopsins, halorhodopsin, and archaerhodopsins enable light-based artificial modulation of neuronal activity in optogenetics.
Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Chemogenetics can be activated via a systemic drug without indwelling fiber optics and acts in a more naturalistic modulatory fashion through second-messenger pathways than optogenetics.
Optogenetic and chemogenetic approaches allow mechanistic, temporally specific, cell-type-specific, and circuit-specific neural regulation of behaviors.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
DREADD technology is presented as the most robust model of chemogenetics.
The study used optogenetic and chemogenetic strategies in peripheral nociceptors to achieve sustained inhibition of pain.
The study developed optoPAIN to examine bidirectional optogenetic and chemogenetic control of pain without physically contacting the animal.
AAV6-hSyn delivery was used to express inhibitory optogenetic and chemogenetic constructs in peripheral afferents.
hM4D(Gi) expression in peripheral afferents increased mechanical and thermal thresholds in a CNO-dependent manner.
iC1C2 produced behavioral inhibition during blue-light illumination in the study.
SwiChR enabled transdermal optogenetic inhibition with sustained post-light inhibition of pain behaviors.
The review context highlights optogenetic and chemogenetic tools as major approaches for manipulating genetically defined amygdala populations in fear-circuit studies.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug designer-receptors-exclusively-activated-by-designer-drug
engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics
Source:
application scopesupports
These optogenetic and chemogenetic toolboxes have enabled advances in deciphering nervous system function and its influence on physiological processes in health and disease.
These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease.
Source:
capability summarysupports
Engineered G protein-coupled receptors activated by otherwise inert drug-like small molecules provide a chemogenetic or pharmacogenetic approach for selective remote control of neuronal activity.
Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics.
Source:
field level assessmentsupports
Optogenetics and pharmacogenetics allow selective and bidirectional modulation of defined neuronal populations with unprecedented specificity.
The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity.
Source:
Comparisons
Source-backed strengths
The cited evidence supports that DREADDs provide selective remote control of neuronal activity through engineered GPCR signaling triggered by otherwise inert ligands. Their value is further supported by inclusion in chemogenetic toolboxes that have enabled advances in nervous system research.
Ranked Citations
- 1.
- 2.
- 3.
- 4.
- 5.