Our Science
The precision gene therapies being developed at Encoded are designed to modulate gene expression within specific cell types to potentially address the underlying disease mechanism.
Disorders of the central nervous system (CNS) contribute to premature mortality and lifelong disability in children and adults globally. Genetic medicines hold potential as a therapeutic modality for treating the root cause of CNS disorders, with an increasing number of gene therapies approved each year.
The Potential of Encoded’s Technology Platform
The brain is the most complex organ in the body with thousands of cell types and trillions of connections called synapses. Most drugs available today affect all cell types in the brain, with limited means to selectively target specific cell types or circuits that are dysfunctional in disease. This can lead to side effects and toxicity, which limit the number of drugs that reach patients.
Encoded’s name comes from the epigenetic code that controls when and where genes are expressed. To that end, we are identifying and optimizing human regulatory elements targeted to specific organs, starting with the brain, that can be harnessed to generate gene therapies with potentially unprecedented selectivity.
Encoded’s Technology Platform
How it works
A gene therapy construct consists of a therapeutic gene, or transgene, and regulatory elements that control its activity, or expression. These include promoters, enhancers and untranslated regions (UTRs). Encoded engineers these regulatory elements to drive precise targeting of specific cell types relevant to disease.
Using genomics-driven screening methods, we screen thousands of naturally-occurring regulatory sequences in the human genome that drive robust and precise gene expression. We then apply machine learning algorithms to these uncovered sequences to identify patterns or motifs that are driving the desired pattern of gene activity.
This enables expression in specific cell types within the brain while minimizing expression in off-target cell types or tissues, for example the dorsal root ganglion, where expression could cause undesirable effects.
Regulatory elements
- Neuron-Specific Expression: Potent and selective neuronal targeting promotes robust gene expression in a cell type implicated in a broad range of neurological and neurodegenerative disorders.
- GABA Cell-Selective Expression: Selective targeting of GABAergic cells unlocks a broad range of neurological disorders characterized by GABA pathway dysfunction, including epilepsy and autism spectrum disorders.
- Dorsal root ganglion (DRG) de-targeting: Transgene expression in the DRG can cause dose-limiting toxicity. 3’UTR DRG de-targeting elements are designed to reduce expression in the DRG with no impact on brain expression.
Customized expression profiles tailored to specific disease states create the potential to maximize therapeutic effect, while minimizing the risk of dose-limiting side effects
Therapeutic Genes
Encoded’s platform also allows for the screening of effectors that can modulate the expression of endogenous genes.
- Engineered transcription factors (eTFs) are designed to increase endogenous gene expression to activate a biological pathway that is deficient in disease states. For this approach, a healthy copy of the gene must be present.
- RNA modulators, such as miRNAs, are designed to drive robust and precise knockdown of pathological gene expression, a common disease driver in neurodegenerative disorders.
Ever wondered what it takes to make a gene therapy?
Join us on a virtual lab tour at Encoded’s headquarters in South San Francisco. Meet a few of our talented scientists ready to explain what goes on behind the scenes as we work to develop potential, transformative therapies.
