Recombinant Cell Platform for Pain Drug Screening

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Solution Overview

Problem

Current methods for identifying drug candidates for pain treatment are hindered by the inaccessibility of neurons that transduce painful stimuli, and primary cells from postmortem neural samples have short lifespans and do not proliferate in vitro, limiting the development of effective pain treatments.

Innovation Solution

A recombinant cell capable of proliferating in vitro, expressing a polypeptide with sequence identity to PRDM12, is used to evaluate drug candidates by assessing electrophysiological, proteomic, transcriptomic, or other characteristics, enabling the identification of effective pain treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If primary cells from postmortem neural samples are used, then the cells can be obtained from human tissue, but the cells have short lifespans and do not proliferate in vitro

Engineering Contradiction:
Improvecell lifespan and proliferative capacityVSAvoidavailability of primary neural cells
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates recombinant neural cells that replicate the functional and phenotypic characteristics of primary nociceptive neurons in vitro. These recombinant cells express pain-related genes and receptors, enabling them to respond to noxious stimuli similarly to primary cells, while overcoming the limitation of primary cells having short lifespans and inability to proliferate.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent modifies cellular parameters by introducing specific recombinant genes (such as PRDM12, NTRK1, or other nociceptive markers) into host cells to transform them into functional nociceptive-like cells. This genetic parameter change enables the cells to exhibit pain-sensing capabilities while maintaining proliferative capacity and extended lifespan in culture.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If neurons that transduce painful stimuli are used, then the cells can directly evaluate pain treatment efficacy, but the cells are inaccessible for in vitro study

Engineering Contradiction:
Improveevaluation of pain treatment efficacyVSAvoidaccessibility of nociceptive neurons
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The recombinant cells serve as intermediary models that bridge the gap between inaccessible primary nociceptive neurons and in vitro drug testing systems. These cells are engineered to express pain-related markers and respond to nociceptive stimuli, allowing researchers to study pain mechanisms and test analgesic drugs in a controlled in vitro environment without needing to access living neural tissue.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent develops in vitro cell models that copy the essential functional properties of nociceptive neurons, including expression of pain receptors (TRPV1, TRPA1), ion channels, and neurotransmitter systems. This copying enables direct evaluation of pain treatment efficacy through electrophysiological recordings, calcium imaging, and behavioral assays in a accessible in vitro platform.

Inventive Principle:
Principle #26Copying

3Reliability

If current pain treatments are used, then pain can be managed, but the treatments are addictive and lose efficacy over time

Engineering Contradiction:
Improvelong-term efficacy of pain treatmentVSAvoidaddiction and tolerance development
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The recombinant cells enable self-contained in vitro pain modeling systems that can continuously evaluate multiple drug candidates without requiring animal models or human clinical trials for initial screening. The cells maintain stable pain-sensing functionality over time, providing a reliable platform for assessing long-term efficacy and safety of potential analgesics without the constraints of animal ethics or human variability.

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS20240302351A1Platform for target discovery and methods of use thereof
Publication Date: 2024.09.12 DOLOROMICS INC

AI summary

Provided herein is a recombinant cell for drug candidate screening. Also provided herein is a method of producing the recombinant cell, and a method of identifying a drug candidate comprising providing the recombinant cell.