Self-Diversifying Polynucleotides for High-Diversity Molecular Libraries

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Solution Overview

Problem

Existing systems lack efficiency and diversity in generating libraries of diversified molecules for screening novel binding partners for antigens and pathogens.

Innovation Solution

A self-diversifying system comprising a polynucleotide encoding one or more open reading frames, including variable and template regions, with a reverse transcriptase, capable of generating a library of diversified molecules with at least 80% efficiency by incorporating mutations into the variable region.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional systems are used to generate diversified molecules, then the process can be performed, but the efficiency is low and the degree of diversity is insufficient

Engineering Contradiction:
Improveefficiency of generating diversified moleculesVSAvoiddegree of diversity of molecules
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The system employs self-diversifying elements that automatically generate diversity through their own molecular mechanisms. The polynucleotide sequences encode for reverse transcriptase enzymes that inherently introduce mutations during reverse transcription, creating diversified molecules without requiring external intervention or complex artificial systems. This self-service mechanism achieves both high efficiency and sufficient diversity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention utilizes error-prone reverse transcription as a parameter change mechanism. By controlling the fidelity of the reverse transcriptase enzyme, the system achieves desired levels of diversity in the generated molecules. The polynucleotide sequences are designed to produce specific mutation rates and types, allowing efficient generation of diversified molecules with controlled variability.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If high diversity is achieved, then the library contains sufficient varied molecules, but the generation efficiency decreases

Engineering Contradiction:
Improvedegree of diversity of moleculesVSAvoidefficiency of generating diversified molecules
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The self-diversifying elements perform the diversity generation function intrinsically through their molecular structure and enzymatic activity. The reverse transcriptase enzymes encoded by the polynucleotides automatically introduce mutations during the reverse transcription process, eliminating the need for separate diversification steps and maintaining high generation efficiency while achieving sufficient diversity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system maintains continuous diversity generation through the ongoing reverse transcription process. The polynucleotide sequences are designed to continuously produce diversified molecules as they are synthesized, rather than requiring discrete diversification steps. This continuous action ensures both high efficiency and adequate diversity in the generated library.

Inventive Principle:
Principle #20Continuity of useful action

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 system effectively generates a diverse library of molecules with high efficiency, enabling rapid identification of binding partners for antigens and pathogens through methods like phage display.

Implementation Method 1

the system is configured to generate a library of diversified molecules with an efficiency of at least 80% as measured by a number of the diversified molecules in a total number of molecules in the library

Methodology Applied
Scientific EffectReverse transcription:

Implementation Method 2

capable of generating a library of diversified molecules with at least 80% efficiency by incorporating mutations into the variable region

Methodology Applied
Scientific EffectMutation:

Data Source

PatentUS12606815B2Self-diversifying systems and methods of use thereof
Publication Date: 2026.04.21 THE BROAD INST INC
  • US12606815B2 patent drawing
  • US12606815B2 patent drawing
  • US12606815B2 patent drawing

AI summary

A diversity-generating system comprising: a polynucleotide comprising: a variable region within a sequence encoding a protein or polypeptide, wherein the system is configured to generate a library of diversified molecules with an efficiency of 80% as measured by number of the diversified molecules in total number of molecules. The system may further comprise a template region; and a reverse transcriptase or functional domain thereof.