RNA-based gene writing in human cells
SCRIBE aims to develop innovative RNA-based gene writing strategies using CRISPR and retrotransposons to enhance gene transfer efficacy and safety for research and therapeutic applications.
Projectdetails
Introduction
CRISPR development has enormously accelerated genetic engineering principles, and precise methods to modify small alleles (such as base or prime editing) are now available. However, generating large genomic changes still presents enormous challenges.
Challenges in Gene Transfer
Large modifications, such as gene transfers, are generally performed with viral vectors, which have been associated with toxicities in the clinic and often lack the versatility needed for basic science experimentation. Newer CRISPR-based techniques for gene transfer suffer from significant efficacy and safety problems when used for large message writing.
Goals of SCRIBE
The overall goal of SCRIBE is to create new strategies for gene writing and define their molecular principles. These new writers will use RNA to both encode and transfer the message.
Mechanism of Action
The SCRIBE strategies will take advantage of the retrotransposon capacity for writing genes from RNA, and the precision of CRISPR in addressing specific sites of the genome. Thus, the “find” function will be dominated by CRISPR components, and “copy-paste” activity will be executed by retroelement components.
Development and Optimization
To develop and optimize such a technology, we will:
- Use evolutionary analysis to select those retroelements with the highest activity and orthogonality.
- Modulate their message writing capacity by engineering their components.
- Test various CRISPR and retrotransposon combinations.
- Adapt both of them to converge into a unified molecular machine.
Application of Artificial Intelligence
We will use artificial intelligence applied to protein design and a novel concept of synthetically oriented evolution to accelerate the emergence of the new function. Finally, we will deploy new gene writing principles for RNA-based in vivo gene delivery.
Conclusion
In sum, we will develop a new family of tools for engineering life. The real breakthrough will be the establishment of gene writing as a simple and general method for both research advancement and applied purposes.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.999.465 |
Totale projectbegroting | € 1.999.465 |
Tijdlijn
Startdatum | 1-5-2024 |
Einddatum | 30-4-2029 |
Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- UNIVERSIDAD POMPEU FABRApenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
Molecular mechanisms, functions and applications of RNA-guided DNA transposonsThis project aims to enhance understanding of RNA-guided DNA transposons to develop advanced genome editing tools for biotechnology and precision medicine. | ERC Starting... | € 1.499.403 | 2024 | Details |
Studying viral protein-primed DNA replication to develop new gene editing technologiesThis project aims to develop novel gene editing technologies by harnessing protein-primed DNA replication from understudied viruses to create efficient, self-replicating protein-linked DNA for therapeutic applications. | ERC Starting... | € 1.641.428 | 2024 | Details |
Transcriptional Engineering of Hematopoietic Stem Cells using CRISPRThis project aims to enhance hematopoietic stem cell therapies by using repurposed CRISPR/Cas systems for precise transcriptional manipulation of key genetic pathways. | ERC Starting... | € 1.499.923 | 2022 | Details |
In Vivo CRISPR-Based Nanoplatform for Gene Editing: A New Disruptive Avenue for Non-Invasive Treatment of Genetic Brain DiseasesThis project aims to develop a novel nanoplatform for the safe and efficient delivery of CRISPR gene editing technology to treat genetic brain diseases non-invasively. | ERC Consolid... | € 2.249.895 | 2022 | Details |
Artificial RNA regulators to probe, control, and design gene regulatory networks in bacteriaThe project aims to utilize artificial small RNAs to explore gene regulation mechanisms and develop synthetic biology tools, focusing on antibiotic resistance and gene network design. | ERC Consolid... | € 1.999.913 | 2023 | Details |
Molecular mechanisms, functions and applications of RNA-guided DNA transposons
This project aims to enhance understanding of RNA-guided DNA transposons to develop advanced genome editing tools for biotechnology and precision medicine.
Studying viral protein-primed DNA replication to develop new gene editing technologies
This project aims to develop novel gene editing technologies by harnessing protein-primed DNA replication from understudied viruses to create efficient, self-replicating protein-linked DNA for therapeutic applications.
Transcriptional Engineering of Hematopoietic Stem Cells using CRISPR
This project aims to enhance hematopoietic stem cell therapies by using repurposed CRISPR/Cas systems for precise transcriptional manipulation of key genetic pathways.
In Vivo CRISPR-Based Nanoplatform for Gene Editing: A New Disruptive Avenue for Non-Invasive Treatment of Genetic Brain Diseases
This project aims to develop a novel nanoplatform for the safe and efficient delivery of CRISPR gene editing technology to treat genetic brain diseases non-invasively.
Artificial RNA regulators to probe, control, and design gene regulatory networks in bacteria
The project aims to utilize artificial small RNAs to explore gene regulation mechanisms and develop synthetic biology tools, focusing on antibiotic resistance and gene network design.
Vergelijkbare projecten uit andere regelingen
Project | Regeling | Bedrag | Jaar | Actie |
---|---|---|---|---|
New Prime Editing and non-viral delivery strategies for Gene TherapyThis project aims to develop non-viral delivery systems and novel prime editors to enhance gene editing efficiency and safety for treating Sickle Cell Disease and other genetic disorders. | EIC Pathfinder | € 4.406.097 | 2022 | Details |
Next generation gene writing platform to cure genetic and oncological diseasesIntegra Therapeutics' FiCAT platform enhances gene therapy by enabling precise and safe insertion of large DNA sequences, aiming to cure genetic and cancer-related diseases. | EIC Accelerator | € 2.496.375 | 2024 | Details |
TraffikGene-Tx: Targeted Peptide Carriers for RNA DeliveryTraffikGene-Tx aims to develop safe, scalable peptide carriers for targeted RNA delivery, addressing genetic diseases and enhancing NAT therapies to improve patient outcomes and reduce healthcare costs. | EIC Transition | € 2.498.963 | 2023 | Details |
FluEdit: Microfluidics Gen-editing platform voor bloedcellenNTrans Technologies ontwikkelt het Flu-Edit platform om efficiënt en veilig gen-editing therapieën voor bloedziekten te realiseren met behulp van microfluidics en iTOP technologie. | Mkb-innovati... | € 20.000 | 2023 | Details |
New Prime Editing and non-viral delivery strategies for Gene Therapy
This project aims to develop non-viral delivery systems and novel prime editors to enhance gene editing efficiency and safety for treating Sickle Cell Disease and other genetic disorders.
Next generation gene writing platform to cure genetic and oncological diseases
Integra Therapeutics' FiCAT platform enhances gene therapy by enabling precise and safe insertion of large DNA sequences, aiming to cure genetic and cancer-related diseases.
TraffikGene-Tx: Targeted Peptide Carriers for RNA Delivery
TraffikGene-Tx aims to develop safe, scalable peptide carriers for targeted RNA delivery, addressing genetic diseases and enhancing NAT therapies to improve patient outcomes and reduce healthcare costs.
FluEdit: Microfluidics Gen-editing platform voor bloedcellen
NTrans Technologies ontwikkelt het Flu-Edit platform om efficiënt en veilig gen-editing therapieën voor bloedziekten te realiseren met behulp van microfluidics en iTOP technologie.