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 develop gene therapies with potentially unprecedented selectivity.
Multiplex staining in the mouse brain. Encoded's cell-selective gene therapy approach enables us to tap into the diversity of different cell types in the brain.
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.
Encoded’s Technology Platform
The Potential
The brain is the most complex organ in the body with thousands of cell types and trillions of connections. Most drug types available today have limited ability to selectively target dysfunctional cell types or circuits, potentially leading to side-effects and toxicity.
Zhao Z, Ukidve A, Kim J, Mitragotri S. Targeting Strategies for Tissue-Specific Drug Delivery. Cell. 2020;181(1):151-167.
Encoded differentiates from current AAV approaches through advanced vector engineering
AAV: Adeno-Associated Virus;
NGS: Next-Generation Sequencing;
UTR: Untranslated Region
High throughput NGS screening platforms and computational modeling optimize payload and regulatory element design
Payload
Engineered protein coding genes, transcription factors, or RNA modulators for diverse gene targeting and modulation
Regulatory Elements (REs)
These include promoters, enhancers and 3′ untranslated regions (3’UTRs)
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 precisely target 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.
Engineered cassette 
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.
AAV: Adeno-Associated Virus;
UTR: Untranslated Region
Engineered cassette Engineered Cassette
Regulatory Elements
Optimized promotors, enhancers, and 3’UTRs drive cell-selective and potent expression while reducing off-target activity.
- 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 expression in the brain.
Potent / cell-selective regulatory elements
De-targeting regulatory elements
Engineered Cassette
Payload
Engineered protein coding genes, transcription factors, or RNA modulators for diverse gene targeting and modulation.
- Protein coding genes are designed to express the coding sequence for an endogenous gene. This can be used to rescue expression of a dysfunctional gene, or overexpress a therapeutic protein.
- 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.
Opportunities
Encoded’s platform has delivered critical innovations supporting the development of gene therapies in monogenic and common CNS 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.
Watch our lab tour.