Annogen’s AIM™ screen revolutionizes the level of control researchers have over transgene expression by identifying optimal genomic loci for transgene integration. Choosing the integration site with the right expression profile will enable safer and more effective cell and gene therapies.
The number of available safe harbor loci is limiting cell therapy engineering
The power of cell therapies relies on stable and controlled expression of therapeutic genes within the engineered cells. Transgenes in these therapies are often integrated with lentivirus or transposases, because these systems are very efficient. However, such random integrations may also result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing. Therefore, targeted integration into a predefined locus is an attractive alternative to random integration and is increasingly used in cell therapies. However, the number of known loci that facilitate safe and correct gene expression (e.g. AAVS1 and TRAC), also referred to a safe harbor loci, is limited.
How to discovery new expression loci
The identification of novel integration sites often involves in silico predictions based on chromatin data, followed by laborious one-by-one targeted integrations to experimentally validate expression characteristics at those loci. AIM™ instead immediately starts with the experimental validation of expression characteristics for hundreds of thousands of potential sites in parallel. AIM™ can be applied to any organism and cell type.
Benefits of AIM™ for cell therapy:
Annogen’s AIM™ screen empowers researchers to overcome the limitations of currently known safe harbor loci by offering a powerful platform for:
- Genome-wide mapping of transgene expression levels: AIM™ comprehensively interrogates reporter genes at >105 unique genomic integration sites.
- Screening based on specific expression pattern requirements: Once an AIM™ cell pool is established, transgene expression levels can be assessed under different conditions such as stimuli of differentiation stages.
- Safe harbor loci identification: Our bespoke AIM™ bioinformatics pipeline can curate identified candidate integration loci based on intersection with e.g. COSMIC or TSGDB, mitigating the risk of integrations with an effect on oncogenes or essential genes.
Accelerate your development with Annogen:
Our team of experts is dedicated to supporting your research and development efforts, as we have done for numerous top biopharmaceutical companies before. We offer a range of services, including custom promoter identification and optimization, licensing opportunities for our proprietary promoters, as well as custom identification of favorable transgene integration sites.
