CMV-Free Porcine Donor Selection for Xenotransplant

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Solution Overview

Problem

Current xenotransplant procedures face challenges in achieving extended survival of transplanted tissues and organs due to immunogenicity issues, particularly with the presence of porcine cytomegalovirus (pCMV) in donor swine, leading to reduced graft survival and increased rejection rates.

Innovation Solution

The method involves selecting CMV-free porcine donors by performing PCR or RT-PCR assays to detect latent or active pCMV, and using these donors for xenotransplant procedures, including skin grafts, to minimize immunogenicity and enhance graft survival.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If xenotransplant tissues are obtained from standard porcine sources, then the procedure is simpler and more readily available, but the transplant survival is reduced and rejection rates increase due to immunogenicity issues

Engineering Contradiction:
Improvetransplant survivalVSAvoiddonor selection process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing PCR-based screening assays on candidate donor swine to detect latent or active pCMV infections before selecting donors for xenotransplantation. This advance detection and selection process identifies CMV-free donors, ensuring that transplants from these selected donors achieve extended survival without accelerated rejection. The screening is performed prior to transplant procurement, allowing only negative candidates to be chosen as donors.

Inventive Principle:
Principle #10Preliminary action

2Duration of action of moving object

If PCR screening is performed on all candidate donors, then rejection rates are reduced and graft survival is extended, but the time and resources required for donor evaluation increase

Engineering Contradiction:
Improvegraft survival durationVSAvoiddonor screening time
Core Design Contradiction:
Duration of action of moving objectVSLoss of time

Solution Approach 1:

The patent extracts and specifically targets the pCMV viral genetic material from candidate donor swine using PCR-based assays. By focusing the screening on detecting only pCMV DNA or RNA sequences rather than performing comprehensive health evaluations, the method efficiently identifies CMV-free donors. This targeted extraction approach minimizes screening time and resources while ensuring that selected donors lack pCMV infection, thereby enabling extended graft survival.

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If CMV-free donors are selected through rigorous screening, then immunogenicity is reduced and transplant survival is extended, but the complexity of the selection process increases

Engineering Contradiction:
ImproveimmunogenicityVSAvoidpCMV detection
Core Design Contradiction:
Object-affected harmful factorsVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces complex serological or cultural methods with PCR-based molecular detection to identify pCMV in candidate donors. The PCR assay specifically amplifies pCMV genetic sequences from blood or tissue samples, providing a highly sensitive and specific detection method. This molecular approach substitutes simpler but less accurate mechanical or visual inspection methods, enabling reliable identification of CMV-free donors and reduction of immunogenicity in xenotransplants.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach results in extended transplant survival and reduced rejection rates, allowing for longer-term temporary coverage of injuries such as burns until allogeneic or autologous grafts can be obtained, with the potential for serial grafting without accelerated rejection.

Implementation Method 1

performing an assay (e.g., a PCR or RT-PCR based assay) on the sample to detect the presence of latent or active porcine cytomegalovirus (pCMV) in the sample

Methodology Applied
Scientific EffectPCR (Polymerase Chain Reaction):

Data Source

PatentUS9883939B2Reducing immunogenicity of xenogeneic transplant tissues
Publication Date: 2018.02.06 THE GENERAL HOSPITAL CORP
  • US9883939B2 patent drawing
  • US9883939B2 patent drawing

AI summary

Methods of preparing and porcine cells, organs and tissues that have reduced immunogenicity, e.g., for transplant into humans, e.g., for the treatment of burn injuries.