Project description
Artificial intelligence takes on nature to discover the secrets of transcription enhancers
All the somatic (non-sex) cells contain all the DNA required to make any of the body's myriad proteins. Obviously, all cells do not make all these proteins. Control of gene expression is regulated in several ways, among them by activation of enhancers. Enhancers are sequences of DNA that, when bound by proteins called transcription factors, boost the transcription of certain genes. Harnessing these could boost the effectiveness of gene therapy. The EU-funded EnhancerDesign project will use AI to figure out enhancer 'logic' and use it for the rational design of synthetic sequences to enhance the transcription of genes in gene therapy. The technology could be widely applicable to therapies for numerous diseases and conditions.
Objective
Gene therapy promises to become a durable clinical option for a whole range of diseases, including monogenic hereditary diseases, cancer and neurodegenerative disorders. However, the development of new gene therapy-based treatments strongly depends on regulatory drivers that provide cell-type specific expression of the transgene, at high enough levels, yet without causing genotoxicity.
The aim of the ERC PoC proposal is to validate a state-of-the-art pipeline, called EnhancerDesign, to design small, strong and cell-type specific human enhancers for gene therapy that will improve specificity and safety, the two major bottlenecks in gene therapy applications. The strength of our EnhancerDesign approach lies in understanding and exploiting the enhancer code by using several state-of-the-art bioinformatics and experimental techniques. We have designed and now aim to validate our pipeline consisting of four parts (1) Single-cell multi-omics profiling; (2) training enhancer models to gain understanding of the enhancer logic; (3) design synthetic sequences in silico; (4) high-throughput enhancer testing.
The project outcome will be twofold. Firstly, the different modules in our pipeline will be further optimized to make the entire pipeline operational to be offered as a service to, or as an asset for collaborative projects with gene therapy companies. Secondly, this project will deliver novel enhancers for a set of chosen cell types, for which no specific enhancers exist, or for which the available enhancers are either too large, too unspecific, or too weak.
Altogether, the development of optimized enhancers by our EnhancerDesign pipeline will allow for improved and cell-type specific expression of a transgene, and has therefore the potential to provide patients with a safer treatment, increased QoL and new treatment options for diseases where gene therapy was not yet an option.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesclinical medicineoncology
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Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
9052 ZWIJNAARDE - GENT
Belgium