Cassette-optimized gene control

AskBio acquired Synpromics Ltd, a leader in gene control synthetic promoter technology, in August 2019. Based on a proprietary data-driven design and bioinformatics, AskBio’s synthetic promoter technology is positioned to make a marked impact on the future of AAV gene therapy. 

We are rapidly advancing the Synpromics AAV promoter technology enabling precise cell and tissue selectivity with inducible capability. The desired result is efficient control of gene expression, regulation of overall gene activity, and increased RNA stability. 

Synthetic promoters are customizable to drive gene expression from therapeutic vectors by leveraging naturally occurring transcriptional elements. As an essential part of our effort to advance gene therapeutics, we can design Synpromics promoters at any length with novel sequences, unique combinations of regulatory elements, and specified activity characteristics.

Promoters are sequences of DNA that sit beside each gene on the genome and whose function is to activate transcription, the initial process whereby a mRNA is synthesized from the gene template. Promoters regulate the activity of genes by controlling a gene’s ability to produce its own uniquely encoded protein.

Synthetic promoters are DNA sequences that do not exist in nature but are unique combinations of naturally occurring transcription response elements that regulate the activity of a target gene with a high degree of selectivity.

Our libraries of synthetic promoters comprise multiple sequence combinations, allowing us to identify stronger and more specific promoters than exist in nature and optimize our promoters for specific functions, aiming to give greater control of how our AAV gene therapies are expressed.

The ability to transcriptionally target and regulate the gene of interest may provide off-target expression which may improve clinical side effects of the final product.

Diagram Expression Cassette
Diagram Expression Cassette

The Synpromics promoter features:

  • Variable protein expression at uncompromised levels in environmental or biological condition
  • Incorporate genetic elements including 5 UTR, Intron, cDNA and 3 UTR
  • Integrate into AAV therapeutics, enabling more effective and accurate next-generation genetic medicines
  • Selective to tissue, single, dual or multiple cell types, developmental stage or cell state
  • Designed to be regulatable, inducible or have a safety switch feature
  • Optimized for size, lower immunogenicity, and to minimize off-target side effects

Synpromics Liver-Selective Promoters

Our liver-specific synthetic promoters offer a wide range of activities. Shown are the results from in vitro luciferase assays for different Synpromics promoters compared to CBA and a benchmark liver promoter. The size of the synthetic promoters ranges from 220 to 545bp.
Our liver-specific synthetic promoters offer a wide range of activities. Shown are the results from in vitro luciferase assays for different Synpromics promoters compared to Chicken Beta Actin (CBA) and a benchmark liver promoter.

Synpromics Muscle-Selective Promoters

Muscle Promoters Box Plot Graph
Our muscle-specific synthetic promoters offer a wide range of activities. Shown are the results from in vitro luciferase assays for different Synpromics promoters compared to a benchmark muscle promoter. The size of the synthetic promoters ranges from 270bp to 1kb.

 






Our muscle-specific synthetic promoters offer a wide range of activities. Shown are the results from in vitro luciferase assays for different Synpromics promoters compared to a benchmark muscle promoter. The size of the synthetic promoters ranges from 270bp to 1kb.
Our muscle-specific synthetic promoters offer a wide range of activities. Shown are the results from in vitro luciferase assays for different Synpromics promoters compared to a benchmark muscle promoter. The size of the synthetic promoters ranges from 270bp to 1kb.

Leading research for precise gene control – Inducible promoters

We are striving to advance gene therapy to complete on/off expression and flexible gene regulation that precisely drives transcription of the target gene. Ultimately, we aim to create a better AAV product with a goal to mprove functional control at any targeted expression level and any cell type. Our efforts include:

  • Tissue-specific gene expression control – inducible with tunable activity levels
  • Repressible capability to turn off constitutive genes
  • In vivo application for any gene therapy vector with inducers and repressors
  • Platform to screen against inducer(s) of choice

Bioinformatics and machine learning

We use comprehensive data-driven resources to gain an in-depth understanding of gene regulation to accurately identify new regulatory sequences from genomes. This enables a unique approach to promoter design and construction that is unparalleled in the industry.

Our proprietary bioinformatics engine, PromPT™, enables highly efficient, data-driven promoter design and specification for a variety of cell types, or in response to environmental, biological or chemical stimuli, potentially leading to effective next-generation cell and gene therapies.

The databases that form part of PromPT are some of the most comprehensive resources developed to understand gene regulation, and we continue to add to this vast data repository to advance our capability for sequencing genome data and machine-based learning. This should enable us to identify and more accurately target new regulatory sequences from genomes, allowing us to take a unique engineering biology approach to promoter design and construction.

AskBio continues to add to a vast data repository to advance our capability for sequencing genome data and machine-based learning.

Prompt Graphic
Prompt Graphic