Abstract:While
engineered chimeric antigen receptor (CAR) T cells have shown
promise in detecting and eradicating cancer cells within patients,
it remains difficult to identify a set of truly cancer-specific CAR-targeting
cell surface antigens to prevent potentially fatal on-target off-tumor
toxicity against other healthy tissues within the body. To help address
this issue, we present a novel tamoxifen-gated photoactivatable split-Cre
recombinase optogenetic system, called TamPA-Cre, that features high
spatiotemporal c… Show more
“…Once familiar with the electronics of this system, there are many ways to customize it. Additional strategies for customizing the system include placing the LED farther or closer to the sample and illuminating through filters/diffusers for homogenous illumination conditions or to prevent heating as in (Supplementary Figure 23) and Allen et al 5 . Another notable feature of our LED design is that it is encapsulated in epoxy and has a touch fastener on the back; this allows the LED to be securely placed with ease virtually anywhere: in incubators, fish tanks, animal cages, walls, etc.…”
Section: Discussionmentioning
confidence: 99%
“…Another potentially critical consideration is to prevent heating (when using the LEDs at high power) or diffusing the light for wider spread illumination. To address these considerations, the LEDs can be mounted outside of a black box with "privacy film" on the inside, as described in Supplementary Figure 23 and Allen et al 5 . Because of the simplicity of this system, taking it apart to verify, modify, upgrade, or repair modular components is not difficult.…”
“…Once familiar with the electronics of this system, there are many ways to customize it. Additional strategies for customizing the system include placing the LED farther or closer to the sample and illuminating through filters/diffusers for homogenous illumination conditions or to prevent heating as in (Supplementary Figure 23) and Allen et al 5 . Another notable feature of our LED design is that it is encapsulated in epoxy and has a touch fastener on the back; this allows the LED to be securely placed with ease virtually anywhere: in incubators, fish tanks, animal cages, walls, etc.…”
Section: Discussionmentioning
confidence: 99%
“…Another potentially critical consideration is to prevent heating (when using the LEDs at high power) or diffusing the light for wider spread illumination. To address these considerations, the LEDs can be mounted outside of a black box with "privacy film" on the inside, as described in Supplementary Figure 23 and Allen et al 5 . Because of the simplicity of this system, taking it apart to verify, modify, upgrade, or repair modular components is not difficult.…”
“…All of these factors bring challenges to drug targets identification. A recent report created a novel system using 4-hydroxytamoxifen and blue light as external inputs, which can realize spatiotemporal control of CAR-T cell activity in solid tumor (Allen et al, 2019). Aiming at personalized medicine, it remains a puzzle that how to control the dose and time of using multidrug.…”
Section: Discussionmentioning
confidence: 99%
“…For example, DNA circuits control CAR expression and T cell activity on the inducible condition of 4-hydroxytamoxifen (Chakravarti et al, 2019). Another novel AND gate system named TamPA-Cre system, which includes inducible Magnet protein domains (nMag, pMag) and split Cre recombinase, can realize localized CAR expression by using 4-hydroxytamoxifen and blue light successively and thus control T cell activation in solid tumor (Allen et al, 2019).…”
Section: Small Molecule Drug-responsive Synthetic Circuits Applied Inmentioning
As a rising emerging field, synthetic biology intends to realize precise regulations of cellular network by constructing artificial synthetic circuits, and it brings great opportunities to treat diseases and discover novel drug targets. Depending on the combination mode of different logic gates, various synthetic circuits are created to carry out multilevel regulations. In given synthetic circuits, drugs often act as inputs to drive circuits operation. It is becoming available to construct drug-responsive gene circuits for experimentally treating various disease models, including metabolic disease, immunity disease, cancer and bacterial infection. Synthetic biology works well in association with the CRISPR system for drug target functional screening. Remarkably, more and more well-designed circuits are developed to discover novel drug targets and precisely regulate drug therapy for diseases.
“…Taking a slightly different approach, several studies used tethering to a cytosolic component to provide tighter regulation of a dimerization-dependent Cre recombinase enzyme. [28,37,38] The studies built on previous work showing that fusion of a steroid hormone ligand binding domain to a protein of interest (POI) can effectively sequester the POI in the cytosol through binding to HSP90. [39] The addition of hormone triggers release of the ligand binding domain from HSP90, allowing entry of the POI into the nucleus.…”
To reveal the underpinnings of complex biological systems, a variety of approaches have been developed that allow switchable control of protein function. One powerful approach for switchable control is the use of inducible dimerization systems, which can be configured to control activity of a target protein upon induced dimerization triggered by chemicals or light. Individually, many inducible dimerization systems suffer from pre‐defined dynamic ranges and overwhelming sensitivity to expression level and cellular context. Such systems often require extensive engineering efforts to overcome issues of background leakiness and restricted dynamic range. To address these limitations, recent tool development efforts have explored overlaying dimerizer systems with a second layer of regulation. Albeit more complex, the resulting layered systems have enhanced functionality, such as tighter control that can improve portability of these tools across platforms.
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