Nanoparticle Deoxyribozyme RNA Splicing for Gene Therapy
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Solution Overview
Problem
Current gene therapy approaches for genetic diseases, such as cystic fibrosis, face challenges in safely editing genes due to the risk of creating cancerous cells and inefficiencies in RNA modification, particularly in splicing nucleic acid sequences.
Innovation Solution
Development of nanoparticles conjugated with catalytically cleaving nucleic acids and an RNA ligating enzyme, like RtcB, to specifically cleave and splice RNA sequences, mimicking the function of the spliceosome, allowing for precise modification of RNA without introducing errors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gene editing approaches (such as CRISPR-Cas9) are used to alter defective genes, then genetic diseases can be treated, but there is a risk of creating cancerous cells due to unintended DNA damage
Solution Approach 1:
The invention extracts the harmful DNA editing step while retaining the beneficial RNA correction function. By using RNA-targeting deoxyribozymes instead of DNA-targeting CRISPR-Cas9, the system corrects RNA sequences without making permanent DNA changes, thereby eliminating the risk of carcinogenic DNA mutations while still treating genetic diseases
Solution Approach 2:
The invention introduces RNA as an intermediary between the genetic defect and the correction mechanism. Instead of directly editing DNA with CRISPR-Cas9, the system uses deoxyribozymes to cleave and correct specific RNA sequences, providing a safer intermediate step that avoids direct genomic manipulation and its associated cancer risks
2Productivity
If conventional RNA modification methods are used, then RNA sequences can be modified, but the splicing efficiency and precision are insufficient
Solution Approach 1:
The invention changes the chemical and catalytic parameters of RNA splicing by using deoxyribozymes with optimized catalytic cores. These engineered nucleic acid catalysts have enhanced cleavage activity and specificity compared to natural ribozymes, improving both the efficiency and precision of RNA splicing through parameter optimization of the catalytic mechanism
Solution Approach 2:
The invention creates composite catalytic systems by combining deoxyribozyme catalysts with nanoparticle carriers. This composite structure integrates the catalytic function of the deoxyribozyme with the delivery and stabilization properties of nanoparticles, enhancing both splicing efficiency and precision while enabling targeted delivery to specific cellular locations
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 method enables efficient and precise splicing of RNA sequences, potentially correcting genetic defects while minimizing the risk of cancerous cell creation, offering a safer and more effective approach for treating genetic diseases.
Implementation Method 1
catalytically cleaving nucleic acids
Implementation Method 2
catalytic hydrolysis of RNA phosphodiester bonds
Implementation Method 3
RNA ligating enzyme, like RtcB
Data Source
AI summary
This disclosure relates to compositions comprising particles conjugated to one or more catalytically cleaving nucleic acids and optionally an RNA ligating enzyme. In certain embodiments, particles reported herein are used for splicing nucleic acid sequences.