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Differential Relays01:20

Differential Relays

Differential relays are used to protect generators, buses, and transformers by comparing electrical quantities at different points. When a fault occurs, the difference in current between the two points triggers the relay to operate, opening the circuit breaker. Under normal conditions, the current entering (i1) and leaving (i2) a generator are equal. When a fault occurs, however, these currents become unequal, and the difference current flows in the relay operating coil, causing the relay to...

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Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor
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Developing and characterizing a two-layered safety switch for cell therapies.

Filippo Rossignoli1,2, Danielle Hoffman1,2, Emaan Atif1,2

  • 1Center for Stem Cell and Translational Immunotherapy (CSTI), Harvard Medical School, Boston, MA, USA.

Cancer Biology & Therapy
|July 13, 2023
PubMed
Summary
This summary is machine-generated.

Engineered cells for therapy can be made safer with a novel double suicide system. This system uses two kill switches, RapaCasp9 and HSV-TK, to control cell elimination and ensure therapeutic safety.

Keywords:
adverse reactioncell therapyclinical translationsafety switchsuicide genes

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Area of Science:

  • Biotechnology
  • Cellular Therapy
  • Cancer Research

Background:

  • Gene-edited cell therapies offer therapeutic potential but raise safety concerns due to cell persistence and toxicity.
  • Existing one-dimensional suicide systems lack comprehensive control over therapeutic cell elimination.

Purpose of the Study:

  • To engineer a robust two-layered suicide system for enhanced safety and controlled elimination of therapeutic engineered cells.
  • To validate the efficacy and reliability of a dual-kill switch system in various cell types and preclinical models.

Main Methods:

  • Engineered therapeutic cells to express two distinct suicide genes: RapaCasp9 and HSV-TK.
  • Activated suicide systems using specific drugs: Rapamycin for RapaCasp9 and Ganciclovir for HSV-TK.
  • Assessed apoptosis induction, cell eradication in vitro and in vivo (subcutaneous and orthotopic models), and sequential activation efficacy.

Main Results:

  • Both RapaCasp9 and HSV-TK demonstrated preserved function and induced apoptosis at distinct time points (24h and 48h) post-activation without observed toxicity.
  • Significant eradication of therapeutic cells was achieved in vivo across different models.
  • Sequential activation of both suicide switches provided improved cell killing, establishing a failsafe mechanism.

Conclusions:

  • The developed double suicide system offers a reliable and effective method for controlling engineered cell populations.
  • This failsafe mechanism enhances the safety profile of cell-based therapies, applicable across diverse cell types and anatomical locations.