US 12,259,378 B2
Dynamic clamps and methods of use thereof
Steven Petrou, Eltham (AU)
Assigned to Praxis Precision Medicines, Inc., Boston, MA (US)
Appl. No. 17/058,978
Filed by Praxis Precision Medicines, Inc., Boston, MA (US)
PCT Filed May 28, 2019, PCT No. PCT/US2019/034171
§ 371(c)(1), (2) Date Nov. 25, 2020,
PCT Pub. No. WO2019/227096, PCT Pub. Date Nov. 28, 2019.
Claims priority of provisional application 62/676,403, filed on May 25, 2018.
Prior Publication US 2021/0215665 A1, Jul. 15, 2021
Int. Cl. G01N 33/487 (2006.01)
CPC G01N 33/48728 (2013.01) [G01N 2333/705 (2013.01)] 7 Claims
 
1. A method of determining whether mutation in an ion channel or a receptor is a gain-of-function or loss-of-function mutation, the method comprising:
a) providing a dynamic clamp in electrical contact with a biological cell or portion thereof comprising a mutant ion channel or receptor for providing a waveform;
b) causing the dynamic clamp to apply a signal based on modulation of the mutant ion channel in the biological cell or portion thereof, thereby providing the waveform at the biological cell or portion thereof; and
c) detecting modulation of the waveform at the biological cell or portion thereof, wherein modulation of the waveform is determined relative to a control, wherein if the modulation of the waveform is increased compared to the control, then the mutation is a gain-of-function mutation, and if the modulation of the waveform is decreased compared to the control, then the mutation is a loss-of-function mutation.