Branched Capped RNA for Faster Ribosome Binding and Translation
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Solution Overview
Problem
Existing capped RNA and circular RNA technologies face challenges in translational activity, with linear RNA requiring further improvements in cap structure introduction and circular RNA exhibiting slow ribosome binding.
Innovation Solution
Introduce a capped RNA structure with branch parts having a cap structure in the upstream region, including hybridization, branched chain, or multi-capped configurations, enhancing translational activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a single cap structure is introduced at the 5′ end of linear RNA, then translation can be initiated, but translational activity requires further improvement
Solution Approach 1:
The upstream region is divided into multiple segments (first upstream region and second upstream region), with cap structures distributed at different positions including the 5′ end and internal locations, allowing enhanced translational initiation from multiple sites rather than a single location
Solution Approach 2:
Multiple cap structures are combined within a single RNA molecule at different positions (5′ end cap and internal cap structures), creating a multi-capped RNA that integrates the functions of multiple cap structures to significantly enhance translational activity
2Productivity
If circular RNA is used without cap structure, then rolling-circle protein translation can occur, but ribosome binding rate is slow
Solution Approach 1:
Cap structures are introduced into the circular RNA molecule in advance (prior to translation), creating pre-cap-modified circular RNA that can immediately enhance ribosome binding rates when introduced into cells, eliminating the need for de novo cap structure formation
Solution Approach 2:
Cap structures are selectively introduced at specific locations within the circular RNA molecule (at the 5′ end of the linearized form or at internal positions), creating localized regions of enhanced ribosome binding capability without altering the overall circular structure
Data Source
AI summary
Provided herein is a capped RNA which has a translated region beginning with a start codon and encoding a protein and an upstream region upstream of the start codon, and a branch part having a cap structure.