Advanced therapeutics across cell and gene therapy face multiple challenges to achieve marketing approval and clinical success, all within the tight time and cost limits of the drug development process.
Traditional approaches rely on viral or endogenous expression systems, often truncated to fit within vector size constraints, these compete with the transcriptional landscape of the cell, particularly where multiple vectors transduce the same cell, leading to complex downstream effects.
Engineered, synthetic promoters based on SynGenSys knowledge driven computational design process, support targeting, dosing, and stability enhancements through informed design and expert curation of promoter options.
We design-in the targeting, expression strength and payload requirements of your therapy, whilst designing out the factors known to contribute to instability and long-term durability limitations.
NK cell-based immunotherapies are critical for treating cancer and immune-related diseases, but current technologies often lack the potency and specificity needed for optimal gene expression and sustained therapeutic effects.
NK.SETTM – Natural Killer Synthetic Expression Technology
Transgene expression levels vary across therapies to optimise therapeutic benefit and meet the specific needs of each disease and patient population.
SynGenSys NK.SETTM contains a library of natural killer cell targeted synthetic promoters with a broad range of activity for titratable therapeutic transgene expression.
NK.SETTM promoters are designed to achieve titratable expression of immunotherapeutic payloads (e.g. CAR, IL-15) relevant to diverse NK cell therapies, such as B-cell malignancies, HER2+ solid tumours and hepatocellular carcinoma.
NK targeted activity and minimal to no off-target expression in B-cell lymphoma and liver cells.
The liver is a crucial target for therapeutic transgene expression in gene therapies of inherited disease such as Hemophilia, Phenylketonuria, and Fabry disease, and in cancer and hepatitis.
Success in liver gene therapies requires promoters that drive transcription at safe and efficacious doses and which supplement safety by minimising or eliminating expression in critical non-target tissues.
Liver.SET delivers tissue-specific, precise, tunable transgene expression with minimal off-target activity in muscle tissue. Demonstrated both in vitro and in vivo for target specificity.
Designed for compatibility with limited vector payload sizes, Liver.SET promoters are significantly smaller than commonly used native or hybrid promoters, maximizing payload availability for therapeutic genes.
Liver.SET promoters are designed specifically to minimize immunogenicity and silencing risks conferred by features such as repeat sequences or CpG islands. and high sequence diversity to limit transcriptional interference and expand access to the transcriptional potential of the cell.
Specific transcription driven by SynGenSys Liver.SET promoters was assessed in vivo relative to generic (CMV) promoter constructs using the AAV9, vector recognized for its broad tropism. Expression was assayed at 3 weeks post injection by RT-qPCR across a range of tissues. Despite the broad tropism of AAV9 vectors, significant expression was detected solely in liver, at levels significantly greater than CMV.
For further details of the development and results achieved for Liver.SET promoters see our White Paper or contact us through the link below to see how our promoter design can support your expression requirements.
Our Muscle.SET library of promoters, developed using SynGenSys proprietary computational selection and design tools, provide broad options for strength of expression and targeting, assessed specifically against HepG2 liver cell lines. The library provides the basis for rapid optimisation for in vivo application and further evolution to meet specific therapeutic requirements.
