Non-Propagating Transgenic Microalgae for RNAi Delivery

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Solution Overview

Problem

Current methods for delivering RNAi molecules, such as dsRNA, to target organisms face challenges including instability and inefficiency, particularly in oral delivery systems, and pose risks of genetic contamination due to propagating transgenic organisms.

Innovation Solution

Development of non-propagating transgenic microalgae that express heterologous RNAi molecules, which are stable and biologically active, allowing for systemic absorption and targeted gene silencing in consumers, and are designed to be environmentally safe by not propagating even if rehydrated.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If propagating transgenic organisms are used for RNAi delivery, then the delivery system can self-replicate and potentially enhance efficacy, but genetic contamination and environmental safety risks increase

Engineering Contradiction:
ImproveRNAi delivery efficacyVSAvoidgenetic contamination
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the harmful propagating capability from the transgenic microalgae by using non-propagating strains that cannot reproduce or form colonies. This removes the genetic contamination risk while preserving the RNAi delivery function, as the microalgae can still be consumed and deliver the RNAi molecules to target organisms.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses non-propagating microalgae as an intermediary delivery vehicle. These microalgae serve as a temporary carrier that delivers RNAi molecules to target organisms through consumption, then is eliminated without reproducing. This intermediary approach enables effective RNAi delivery while preventing genetic contamination of the environment.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If RNAi molecules are delivered through conventional methods, then direct delivery to target organisms is possible, but stability and biological activity are reduced during processing and consumption

Engineering Contradiction:
ImproveRNAi molecule stabilityVSAvoidRNAi molecule integrity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent utilizes the microalgal cell wall and membrane structures as protective shells that encapsulate and protect the RNAi molecules during processing and digestion. These biological membranes provide physical protection and maintain RNAi molecule integrity until they are released in the target organism, thereby enhancing stability without requiring synthetic encapsulation materials.

Inventive Principle:
Principle #30Flexible shells and thin films

3Ease of operation

If transgenic microalgae are used as RNAi delivery vehicles, then oral delivery to target organisms is enabled, but the complexity of creating and maintaining transgenic lines increases

Engineering Contradiction:
Improveoral delivery capabilityVSAvoidtransgenic microalgae development
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent develops a universal non-propagating microalgal platform that can deliver RNAi molecules to various target organisms (insects, fish, mammals) through a common mechanism of consumption and digestion. This multi-functional platform reduces the need to develop separate delivery systems for different targets, thereby simplifying the overall approach despite the initial complexity of creating transgenic lines.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 RNAi molecules remain intact and functional during processing and consumption, effectively silencing target genes in organisms, while the non-propagating microalgae prevent genetic contamination, offering a generic and safe delivery method for various organisms.

Implementation Method 1

systemic absorption and targeted gene silencing in consumers

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Data Source

PatentUS11939576B2Transgenic microalgae and use thereof as a feed for delivery of interfering RNA molecules
Publication Date: 2024.03.26 TRANSALGAE ISRAEL
  • US11939576B2 patent drawing
  • US11939576B2 patent drawing
  • US11939576B2 patent drawing

AI summary

The present invention provides non-propagating transgenic microalgae expressing at least one heterologous RNAi molecule. The RNAi-expressing non-propagating transgenic microalgae are used for oral delivery of the RNAi molecule to a target organism in its intact and functional form. The heterologous RNAi molecule, present within the microalgae, is characterized by being biologically active, exerting at least one specific effect on the organism consuming the microalgae or on a pathogen of said organism. In particular, the non-propagating transgenic microalgae are used as agents for biological control of animal and plant pests.