Reimagining AAV, the Ultimate Bioengineered
Delivery Vehicle
Adeno-associated viruses (AAVs) are non-pathogenic viruses that can be engineered to deliver DNA to drive the endogenous production of therapeutic proteins within specific target tissues. By programming cells to produce particular proteins, AAV gene therapies can convert transduced cells into local “biofactories” for these therapeutic proteins to achieve the desired clinical effect.
Advantages of AAV gene therapy
- AAVs are non-pathogenic viruses that have been studied extensively in clinical settings, with substantial existing clinical safety experience
- AAVs have been demonstrated to have lower immunogenicity compared to other viral vectors
- AAVs have the potential to deliver durable, even lifelong clinical benefit following one-time administration (a “one-and-done” effect)
- AAVs are suitable for direct-to-tissue delivery, enabling direct injection into the relevant site of pathology or desired biological activity
We believe in the potential of gene therapy to address a broad range of diseases. We view AAV as the ultimate delivery vehicle to drive the durable endogenous production of therapeutically relevant proteins, when rationally and deliberately engineered.
SIRVETM: our proprietary intelligent vector design platform
SIRVE (System for Intelligent Rational Vector Engineering) is our technology-enabled platform for de novo vector design, sequence modification, and data analysis. We marry computer science with the latest developments in vector biology to minimize immunogenicity, improve tissue specificity, and enhance the expression and manufacturability of our gene therapies. SIRVE is built for modularity, to enable the targeted focal production of desired therapeutic proteins using rationally engineered AAV vectors.
Reduced Immunogenicity
Minimizing the presence of immunostimulatory features through targeted sequence modification
Enhanced Expression
Selecting the optimal capsid for target tissue transduction, and engineering cassettes to achieve robust expression
SIRVE
Improved Tissue Specificity
Combining novel design elements with focal delivery techniques to achieve selective expression within the relevant tissue
Improved Manufacturability
Engineering the vectors to achieve maximal packaging efficiency while minimizing impurities within the final product
SIRVE
Reduced Immunogenicity
Minimizing the presence of immunostimulatory features through targeted sequence modification
Enhanced Expression
Selecting the optimal capsid for target tissue transduction, and engineering cassettes to achieve robust expression
Improved Tissue Specificity
Combining novel design elements with focal delivery techniques to achieve selective expression within the relevant tissue
Improved Manufacturability
Engineering the vectors to achieve maximal packaging efficiency while minimizing impurities within the final product
Optimizing the Expression Cassette
We take a methodical approach to de novo vector design and targeted sequence modification to engineer and optimize our therapeutic constructs.
Promoter
The promoter is a regulatory element that drives expression of the transgene. Selection of the appropriate promoter is critical to achieving robust and durable expression in the desired tissue.
Open Reading Frame
The open reading frame (ORF) includes the transgene that encodes for the desired protein product. In engineering the ORF, it is important to minimize the presence of immunostimulatory motifs, utilize strong and appropriate signaling elements, and ensure the generation of optimally folded and functionally active proteins.
PolyA
The Polyadenylation (PolyA) signal is located at the end of the expression cassette and promotes the stability and longevity of the transcript.
ITR
The ITRs demarcate the DNA sequence and play a key role in its packaging into the AAV capsid particles. The ITRs also play a critical role in the formation of concatemers that ensure long term transgene expression following AAV delivery to human subjects. Maintaining consistency and integrity of the ITRs is critical throughout the production process.
Backbone
The backbone is a part of the plasmid DNA that is used in the production of AAV but does not serve a functional purpose in the final drug product. Nevertheless, portions of the backbone often get packaged into the final product and are considered impurities. Rational engineering of the backbone can help reduce the degree of plasmid backbone packaging and the potential immunogenicity associated with such impurities.
Our Pipeline
We focus on developing gene therapies for diseases with well-understood biology and established clinical endpoints, and where the durable expression of a particular therapeutic protein could have a transformative clinical impact. We select targets for which we anticipate a manageable total AAV dose is required to have the desired therapeutic effect. Our pipeline includes internally developed products as well as programs originated at leading academic institutions around the world.
KT-A112 - Type 1 Diabetes
Metabolic Disease
KT-A281 - Solid Tumors
Immuno-Oncology
KT-A252 - Geographic Atrophy
KT-A261 - Uveitis