LDHA Gene Editing for Hyperoxaluria Oxalate Reduction
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Solution Overview
Problem
Hyperoxaluria, a rare genetic disorder leading to excessive oxalate production, results in kidney damage, urinary stones, and end-stage renal disease, with current treatments like renal dialysis or organ transplant being the only options, and existing methods for reducing oxalate production have adverse effects.
Innovation Solution
Utilizing CRISPR/Cas system-guided RNA to target and silence the LDHA gene, reducing LDH expression, thereby decreasing oxalate production and increasing glycolate levels, offering a long-term treatment for hyperoxaluria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If renal dialysis or organ transplant is used to treat hyperoxaluria, then kidney failure and end-stage renal disease are prevented, but the treatment options are limited and complex procedures are required
Solution Approach 1:
The patent replaces mechanical/physical treatment methods (dialysis, transplant) with a molecular biology approach using CRISPR/Cas9 gene editing to directly modify the LDHA gene, eliminating the need for complex mechanical treatment systems
Solution Approach 2:
The patent extracts and targets the specific problematic gene (LDHA) responsible for oxalate production, separating the treatment from the need for organ-level interventions like dialysis or transplant
2Quantity of substance
If existing methods for reducing oxalate production are used, then oxalate levels decrease, but adverse effects occur
Solution Approach 1:
The patent applies localized gene editing specifically to the LDHA gene in liver cells, targeting only the source of oxalate production while preserving other liver functions and avoiding systemic adverse effects
Solution Approach 2:
The patent replaces conventional pharmacological or dietary methods with precise CRISPR/Cas9 gene editing, achieving oxalate reduction through molecular mechanism rather than systemic treatment that causes adverse effects
3Reliability
If LDHA gene editing is performed, then oxalate production is reduced and kidney damage is prevented, but the method requires delivery of CRISPR/Cas system components to liver cells
Solution Approach 1:
The patent uses lipids as intermediary carriers to deliver CRISPR/Cas9 components to liver cells, enabling efficient gene editing without requiring complex surgical or invasive procedures
Solution Approach 2:
The patent replaces complex delivery systems with a simplified lipid-based molecular delivery mechanism, making the gene editing process more feasible and scalable
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
The CRISPR/Cas system effectively reduces oxalate production, preventing calcium oxalate deposition and kidney damage, while maintaining liver function, and potentially delaying the need for kidney or liver transplant.
Implementation Method 1
Utilizing CRISPR/Cas system-guided RNA to target and silence the LDHA gene
Implementation Method 2
a guide RNA comprising a guide sequence that is at least 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or 90% identical to a sequence selected from SEQ ID NOs: 1-84 and 100-192
Data Source
AI summary
Compositions and methods for editing, e.g., introducing double-stranded breaks, within the LDHA gene are provided. Compositions and methods for treating subjects having hyperoxaluria are provided.