TREMs for Contextually Rare Codon Translation

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Solution Overview

Problem

Current methods fail to effectively modulate the production parameters of RNAs or proteins encoded by RNAs with contextually rare codons, which are limiting due to the availability of corresponding tRNAs, leading to unaddressed diseases and disorders.

Innovation Solution

Administration of a tRNA effector molecule (TREM) composition corresponding to contextually rare codons to target cells or tissues, modulating the production parameters of RNAs or proteins by increasing or decreasing their expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional translation methods are used, then protein production proceeds with standard codon usage, but contextually rare codons cause limited protein production due to insufficient tRNA availability

Engineering Contradiction:
Improveprotein productionVSAvoidtRNA availability
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent introduces synthetic tRNA molecules as intermediary substances that mediate between the ribosome and the contextually rare codons. These synthetic tRNAs carry the specific amino acids corresponding to rare codons and deliver them to the ribosome, effectively bridging the gap caused by natural tRNA scarcity and enabling efficient translation of rare codons.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the parameter of tRNA abundance by introducing synthetic tRNAs that are not naturally present in the cell at high concentrations. This parameter change (increasing tRNA abundance for rare codons) directly resolves the limitation and enables efficient protein production from mRNAs containing contextually rare codons.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If genes with contextually rare codons are expressed, then diverse protein functions can be achieved, but production parameters remain limited due to translational bottlenecks

Engineering Contradiction:
Improveprotein function diversityVSAvoidprotein production parameter
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

Synthetic tRNAs serve as mediators that enable the expression of genes with contextually rare codons without limiting protein production. By providing abundant synthetic tRNAs for rare codons, the system maintains the ability to produce diverse protein functions while eliminating the translational bottleneck that would otherwise restrict productivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If endogenous tRNA pools are relied upon, then natural translation occurs, but contextually rare codons create unaddressed diseases and disorders

Engineering Contradiction:
Improvenatural translationVSAvoidprotein production
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent introduces synthetic tRNAs as complementary intermediaries to the endogenous tRNA pool. These synthetic tRNAs specifically address the deficiency for contextually rare codons while working alongside natural tRNAs, thereby maintaining reliable translation for common codons while resolving the productivity issues caused by rare codon scarcity.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 TREM composition effectively modulates the expression of RNAs or proteins encoded by RNAs with contextually rare codons, addressing diseases and disorders by improving protein production parameters.

Implementation Method 1

Transfer RNAS (tRNAs) are molecules which possess a number of functions including the initiation and elongation of proteins

Methodology Applied
Scientific EffectTranslation:

Data Source

PatentUS20220364092A1TREM compositions for con-rare codons and related uses
Publication Date: 2022.11.17 FLAGSHIP PIONEERING INNOVATIONS VI LLC
  • US20220364092A1 patent drawing
  • US20220364092A1 patent drawing
  • US20220364092A1 patent drawing

AI summary

The invention relates generally to uses of tRNA-based effector molecules (TREMs) corresponding to con-rare codons and methods of making the same.