Search

CN-122000049-A - Drug targeting treatment effect verification system based on transgenic mouse model

CN122000049ACN 122000049 ACN122000049 ACN 122000049ACN-122000049-A

Abstract

The invention belongs to the technical field of biological medicine, in particular relates to a drug targeting therapeutic effect verification system based on a transgenic mouse model, and discloses a drug therapeutic effect verification system integrating genetic engineering modeling, multi-mode sensing and AI data fusion. The system adopts humanized immunity and controllable pathogenic gene modified transgenic mice, combines an implanted multifunctional biosensor array, realizes in-situ dynamic monitoring of drug concentration, target point response and microenvironment change, and synchronously acquires physiological and behavioral multidimensional data. And carrying out space-time alignment and fusion analysis by a deep learning engine to generate a quantitative evaluation matrix containing pharmacodynamics and off-target risks, and supporting closed-loop feedback regulation drug delivery. The problems of poor predictability and single static detection means of the traditional model are solved, and the efficiency and the clinical transformation accuracy of new medicine research and development are remarkably improved.

Inventors

  • LI ZHENZHEN

Assignees

  • 李真真

Dates

Publication Date
20260508
Application Date
20260115

Claims (10)

  1. 1. A drug-targeted therapeutic effect verification system based on a transgenic mouse model, comprising: the genetic engineering modeling unit is used for constructing a transgenic mouse biological vector which carries a mutant gene related to human diseases and completes humanization transformation at a key immunoregulatory site; The multifunctional biological sensing unit is used for implanting a miniaturized sensor array in a specific organ or tumor microenvironment of the transgenic mouse so as to perform in-situ continuous dynamic acquisition on key pharmacological parameters in a local microenvironment; the wireless signal transmission unit is used for transmitting the digitized physiological signals acquired and conditioned by the multifunctional biological sensing unit to an external data convergence gateway through a near field communication protocol; The behavior observation unit is used for synchronously recording the three-dimensional motion trail, the body temperature rhythm change and the ultrasonic sounding characteristics of the transgenic mice in the acoustic isolation cabin; The multi-source information fusion engine is used for receiving the time-space alignment data streams from the wireless signal transmission unit and the behavior observation unit, performing cross-mode joint modeling by adopting a deep learning architecture and outputting a quantized curative effect evaluation matrix; And the closed-loop feedback adjustment module is used for generating an adaptive intervention instruction according to the quantized curative effect evaluation matrix and driving an external execution device to adjust a drug administration strategy or activate a physical synergy device.
  2. 2. The drug-targeted therapeutic effect verification system based on a transgenic mouse model according to claim 1, wherein the genetic engineering modeling unit is used for implementing triple-level genetic modification on a C57BL/6N background system by a CRISPR-Cas12a synergetic homology directed repair technology, wherein a point mutation sequence completely consistent with a human cancer driving gene is introduced in a first level, a tetracycline inducible promoter is accessed in an upstream regulatory region, a complete set of human leukocyte antigen class II molecule coding sequences and corresponding transcriptional regulatory elements are inserted in a chromosome safe harbor site fixed point in a second level, and nonsense mutation editing is performed on an endogenous Fc receptor gene in a third level.
  3. 3. The drug targeting therapeutic effect verification system based on a transgenic mouse model according to claim 2, wherein the multifunctional biosensing unit comprises a two-dimensional gradient arrangement array formed by a plurality of microelectrode units, and molecular probes corresponding to target drug molecules, target protein phosphorylation forms and key metabolic byproducts are covalently immobilized on the surface of each microelectrode unit, and comprise an aptamer, a single-chain antibody fragment and a synthetic peptide receptor.
  4. 4. The drug-targeted therapeutic effect verification system based on a transgenic mouse model according to claim 3, wherein the multifunctional biosensing unit further comprises a miniature temperature compensation circuit and a miniature reference electrode integrated in each microelectrode unit, and an embedded low-power-consumption signal conditioning module for noise suppression and digital conversion of original signals.
  5. 5. The drug targeting therapeutic effect verification system based on the transgenic mouse model of claim 4, wherein the behavior observation unit comprises a three-dimensional motion capture system consisting of a plurality of high-speed infrared cameras, an infrared thermal imager arranged at the top of a cabin body, a voiceprint acquisition device covering an ultrasonic frequency band and a pressure sensitive film paved at the bilge.
  6. 6. The drug-targeted therapy effect verification system based on the transgenic mouse model of claim 5, wherein the multi-source information fusion engine comprises a graph neural network module, a time convolution network module and an attention mechanism module, wherein the graph neural network module is used for treating different types of sensor nodes and behavior characteristics as vertexes in a graph structure and establishing edge connection based on physiological coupling strength, the time convolution network module is used for processing time sequence characteristics, and the attention mechanism module is used for dynamically weighting fused high-dimensional characteristic vectors.
  7. 7. The drug-targeted therapy effect verification system based on a transgenic mouse model according to claim 6, wherein the multi-source information fusion engine further comprises a pre-trained pathology progress simulator for dynamically comparing the dynamic feature vector of the real-time observation data with a standard template of the historical drug action mode, and calculating a deviation index to trigger an early warning mechanism.
  8. 8. The drug-targeted therapeutic efficacy verification system based on a transgenic mouse model according to claim 7, wherein the multi-source information fusion engine is further configured to perform a reverse reasoning function to trace back to infer the most likely affected brain neural circuit or peripheral organ functional state based on the observed behavioral abnormal combination.
  9. 9. The drug-targeted therapy effect verification system based on a transgenic mouse model according to claim 8, wherein the closed-loop feedback adjustment module comprises a decision logic engine for jointly judging a system operation state according to a plurality of indexes in the quantitative therapy effect evaluation matrix, and switching to a dose down-regulation state, a physical synergy state or an emergency medicine state when the system operation state meets a preset condition.
  10. 10. The drug targeting therapeutic effect verification system based on a transgenic mouse model according to claim 9, wherein the closed-loop feedback adjustment module is used for activating a focused ultrasound transducer array pre-implanted in peripheral tissues of a tumor in a physical synergistic state to generate an instantaneous cavitation effect at a specific coordinate position to promote vascular permeability, and is used for broadcasting a hard interrupt instruction to all relevant devices and starting an emergency plan in an emergency stop state.

Description

Drug targeting treatment effect verification system based on transgenic mouse model Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a drug targeting treatment effect verification system based on a transgenic mouse model. Background In the field of biomedical research and development, preclinical validation of drug targeted therapy is a key link for determining success and failure of new drug development. The field covers a plurality of branches such as drug design, target spot screening, drug effect evaluation and the like, and the core aim is to ensure that the drug can specifically act on lesion cells or tissues and simultaneously reduce toxic and side effects on normal tissues to the greatest extent. In the process, the animal model is used as an important bridge for connecting in-vitro experiments and clinical experiments, plays a core role in simulating human pathological environments and evaluating in-vivo behaviors of medicines, and the scientificity and the reliability of the animal model are directly related to the accuracy of subsequent research and development decisions. The disease model constructed based on the transgenic mice can accurately simulate pathological features caused by human specific gene mutation, and is widely applied to pharmacodynamics research in the fields of tumor, genetic diseases, immune system diseases and the like. The model enables the mice to express human pathogenic genes or knock out specific functional genes through a gene editing technology, so that the molecular mechanism and the phenotypic characteristics of diseases are reproduced at the living body level, and an ideal biological platform is provided for dynamic observation of drug targeting and therapeutic effects. In the prior art, although construction and basic pharmacological test of a transgenic mouse model are realized, the method still has obvious defects in the aspect of verification of systematic and standardized drug targeting therapeutic effects, such as lack of synchronous acquisition and association analysis capability of multidimensional drug effect indexes (such as target organ drug enrichment degree, focal area apoptosis rate and systemic toxic reaction), difficult effective correction of interference of biological differences among model individuals on experimental results, and the traditional evaluation flow depends on manual interpretation and discretization detection means, so that data repeatability is poor and verification period is long. In addition, the whole process from drug administration intervention to end point analysis lacks a unified data management architecture, can not support transverse comparison and statistical modeling of experimental results of multiple batches and multiple centers, and severely restricts drug development efficiency and conversion success rate. Therefore, it is needed to construct an integrated drug targeting therapeutic effect verification system based on a transgenic mouse model to solve the technical bottleneck. Disclosure of Invention The invention aims to provide a drug targeting therapeutic effect verification system based on a transgenic mouse model, so as to solve the problem of huge transformation gap between an in-vitro cell experiment and a human clinical experiment in the current drug research and development process. The prior art generally relies on traditional animal models or simple gene knockout mice for primary screening of drug effects, however, the models are difficult to truly simulate the complex genetic background and pathological microenvironment of human diseases, so that a large number of candidate drugs with excellent performance in animal experiments fail in the subsequent clinical stage. In addition, conventional detection means are mostly focused on end point type physiological index measurement, lack of real-time and multidimensional monitoring capability on the dynamic process of the drug action, and cannot accurately analyze drug targeting, tissue distribution characteristics and molecular response mechanisms. The defects obviously prolong the research and development period of the medicine, improve the research and development cost and limit the development of accurate medical treatment. The technical scheme of the invention is that a comprehensive verification system integrating genetic engineering modeling, multi-mode biosensing, automatic behavior analysis and artificial intelligent driving data fusion platform is constructed. The system uses transgenic mice carrying human disease related mutant genes and subjected to humanized modification at key immunoregulatory sites as a biological carrier, and realizes continuous dynamic acquisition of key pharmacological parameters in local microenvironments by implanting miniaturized and long-term stable multifunctional biosensor arrays in specific organs or tumor microenvironments. The sensor array has a molecular