Our Approach to Genetic Medicine

Next-Generation Vector Optimization

Genetic medicines use a delivery vehicle, referred to as a vector, to insert a gene encoding for a therapeutic protein into cells in the body. Together with bespoke design of our gene therapy vectors through extensive optimization of all the vector’s components, MeiraGTx is employing multiple platforms for assessing potency and safety. We believe that by testing our novel genetic medicines in relevant animal models as well as in patient-derived human organoids (retinal and brain), we increase the probability of success in selecting the more efficacious and safe candidate for clinical development.

The key components of a vector

The Gene

The gene encodes the therapeutic protein

The Capsid

The outer viral protein shell that encloses the gene and is responsible for binding to the cell surface, allowing the gene to enter the cell

The Promoter

The DNA sequence that drives the expression of the gene

Vector Optimization

Customization of the vector allows for gene therapy to be optimized for different diseases and can have a significant impact on the effectiveness and safety of the treatment.

Promoters can drive different levels of gene expression or restrict gene expression to specific cell types. Other aspects of the gene sequence may be engineered for optimal gene expression and reduced immunogenicity.

Leveraging our genetic medicine platform technologies, we are able to customize many of these vector elements in order to design a product candidate specific to the disease being targeted. This customization differentiates our approach to developing and delivering genetic medicines.

Promoter Discovery

Promoters, the regulatory DNA sequences that control gene expression, are a crucial component of any vector. They determine where and how much a therapeutic gene is expressed, making them essential for the safety and efficacy of gene therapies.

MeiraGTx’s promoter discovery group combines rational design, high-throughput screening, and AI/ML to develop novel promoters and enhancers tailored to specific therapeutic needs.

Complementing our rational design efforts, we utilize high-throughput screening platforms to evaluate vast libraries of promoter variants. The data generated from our screens is then fed into ‘CLARA’, MeiraGTx’s proprietary Convolutional Neural Network (CNN) model for in-silico prediction of promoter activity, enabling machine-guided design of novel promoters with unprecedented potency. Top performing promoters are then characterized and validated across multiple translationally-relevant models, including in human organoids.

Our efforts have led to the discovery of both cell-specific and ubiquitous promoters, as well as potent mini promoters which allow inclusion of larger therapeutic genes or additional regulatory elements. As we continue to push the boundaries of promoter engineering, we are also uncovering new insights into the fundamental principles of gene regulation.

Together with our proprietary Riboswitch platform, we are able to design genetic medicines with unprecedented control over the timing, level, and location of gene expression.

Next-Generation AAV Capsids

We are combining rational design and directed evolution screens, conducted directly in non-human primates, to discover next-generation adeno-associated virus (AAV) capsids with improved transduction and safety profiles.

In the eye, our screening efforts for improved intravitreal capsids have yielded multiple promising capsids with significantly improved transduction profile compared to the best clinically validated intravitreal capsids, targeting the front (ciliary body) or back of the eye.