CELL THERAPY SOLUTIONS

PROMOTER DISCOVERY
OPTIMAL EXPRESSION

For a gene therapy to be effective, it is important to target the gene expression of a vector to specific cell types, optimising therapeutic transgene expression and avoiding off-target effects. The use of novel promoters provides a way to create exacting levels of gene expression, under tight local and temporal control.

We offer promoter discovery services for optimal on-target therapeutic gene expression. Our promoter discovery team will fine-tune the expression and localisation of your therapeutic transgene with benefits for viral vector utility, safety and efficacy, optimizing the performance of your novel therapeutic.

We work closely with customers to understand their precise gene expression requirements, using bioinformatic tools to ensure that we identify the best promoters for a novel therapeutic.

Getting the level of gene expression just right

We are experienced in matching transgene expression to physiological levels, reducing the risk of toxicity caused by severe overexpression. Our ability to target expression to specific tissue types helps prevent off-target effects. We also provide opportunities to specifically express the therapeutic transgene in response to specific environmental or developmental cues.

A bioinformatics-led approach

We use a bioinformatics-informed approach to design and discover promoters that are not found in nature. OXGENE’s synthetic promoter libraries are generated using bioinformatics-associated rational design and aided by proprietary in-house algorithms. We can synthesise a range of core promoters and assemble them with enhancers to form unique combinations for targeted gene expression.

eGFP-tagged libraries are barcoded such that each promoter-enhancer combination is linked to a specific barcode. These libraries are then packaged into lentivirus which is used to transduce the relevant cell type. After cells are sorted and enriched for active promoters using flow cytometry on eGFP, specific barcodes can be identified by next-generation sequencing and novel promoter-enhancer combinations can be identified.

Screening for novel promoters

A combinatorial promoter library, tagged with eGFP, is packaged into lentivirus and expressed in a tissue-specific cell type. Cells are expanded and enriched for active promoters using flow cytometry on eGFP. Cells containing active promoters are then sequenced by next-generation sequencing, before bioinformatic analysis is used to identify the novel synthetic tissue-specific promoters.

Cell-type specific promoter activity

OXGENE’s synthetic promoters show cell-specific activity, demonstrating that they are highly targeted for the cell type of choice. OXGENE can work with a range of target cell types, covering diverse therapeutics.

OXGENE’s synthetic promoters show cell-specific activity

For two active promoters, specific activity is observed in Jurkat cells and at much lower levels in other cell types including non-lymphocytic cell lines.

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