Cassette-optimized gene control

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

We are rapidly advancing the Synpromics AAV promoter technology into the clinic enabling precise cell and tissue selectivity with inducible capability. The 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 and yield many patient benefits. Essential to advancing 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 protein 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 novel combinations of naturally occurring transcriptional elements that regulate the activity of a target genes 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, giving greater control of how our AAV gene therapies are expressed.

The ability to transcriptionally target and regulate the gene of interest provides an extra layer of safety to AAV gene therapies, preventing off-target expression and reducing potential side effects of the treatment.

The Synpromics promoter advantages:

Variable protein expression at uncompromised levels in any environmental or biological condition
Incorporate all genetic elements including 5 UTR, Intron, cDNA and 3 UTR
Integrate into novel self-complementary AAV therapeutics, enabling more effective, safer 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, lowers immunogenicity, and reduces 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.

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.

Precise gene control – Inducible promoters

A powerful and necessary advancement in gene therapy will be 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 by improving 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 the most 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 any cell type, or in response to any environmental, biological or chemical stimuli, enabling more 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 enables us to identify new regulatory sequences from genomes with a higher degree of accuracy, allowing us to take a unique engineering biology approach to promoter design and construction.

“We continue to add to a vast data repository to advance our capability for sequencing genome data and machine-based learning.”

Partner with RhiaPharmaceutical