Modular RNA Nanostructures for Stable Tumor-Targeted Delivery
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Solution Overview
Problem
Existing RNA delivery technologies face challenges such as susceptibility to nuclease digestion and inefficient targeting of tumor and immune cells, limiting their effectiveness in treating diseases like cancer and infectious diseases.
Innovation Solution
Development of modular RNA delivery platforms, including multivalent RNA oligonucleotide junction complexes and nucleic acid nanodevices, that facilitate rapid and targeted delivery of siRNA, shRNA, and mRNA to tumor and immune cells, utilizing complementary RNA oligonucleotides and targeting molecules to enhance specificity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dsRNA is used as an adjuvant in vaccines, then immune response is enhanced, but susceptibility to nuclease digestion increases
Solution Approach 1:
The patent introduces a delivery platform (such as lipid nanoparticles or conjugates with targeting molecules) as an intermediary carrier to protect dsRNA from nucleases while delivering it to target cells. This mediator system allows the dsRNA to maintain its immunostimulatory function without direct exposure to degrading enzymes in the circulation.
Solution Approach 2:
The patent modifies the chemical or physical parameters of dsRNA through conjugation with targeting molecules, PEGylation, or incorporation into protective carriers, which changes its stability profile against nucleases while preserving or enhancing its immunological activity.
2Productivity
If conventional RNA delivery methods are used, then delivery is achieved, but targeting specificity to tumor and immune cells is insufficient
Solution Approach 1:
The patent applies local quality by incorporating cell-specific targeting molecules (such as antibodies, aptamers, or peptides) on the surface of the delivery platform, which are selectively expressed or bound by specific cell types like tumor cells or immune cells, thereby achieving localized delivery to the desired target.
Solution Approach 2:
The delivery platform is segmented into functional components: a core delivery vehicle (e.g., nanoparticle) and surface-functionalized targeting moieties. This segmentation allows independent optimization of delivery efficiency and targeting specificity through modular design.
3Adaptability or versatility
If RNA therapeutics are delivered systemically, then broad coverage is achieved, but susceptibility to degradation and off-target effects increases
Solution Approach 1:
The patent employs a protective intermediary carrier system that circulates in the bloodstream, shielding RNA therapeutics from degradation while maintaining circulation time. This mediator enables systemic distribution without compromising RNA stability or causing off-target effects.
Solution Approach 2:
The patent incorporates mechanisms such as cell-penetrating peptides or stimuli-responsive releases that provide feedback based on the cellular environment, allowing the delivery system to activate or release cargo specifically in response to tumor or immune cell signals, thereby reducing off-target effects.
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 platforms enable direct tumor killing and immune response induction by effectively delivering RNA therapeutics to targeted cells, enhancing treatment efficacy for cancers like colorectal, pancreatic, breast, ovarian, lung, and melanoma, as well as inducing immune responses.
Implementation Method 1
utilizing complementary RNA oligonucleotides and targeting molecules to enhance specificity and stability
Data Source
AI summary
Described herein are mRNA carrier systems and methods of their use for entering the cytoplasm and expressing carried mRNA, to induce a tumor killing effect. The mRNA carrier systems can comprise DNA or RNA nanostructures. Also described herein are methods of treating cancer using the mRNA carrier systems described herein.