Precision base editing unlocks new potential for in vivo gene therapies.

A recent New England Journal of Medicine publication on NTLA-2002 marks a historic milestone: a CRISPR-based in vivo base editing therapy tailored to an individual that significantly reduced attacks associated with hereditary angioedema¹. It’s a powerful demonstration of what gene editing can achieve in the clinic. So, how do we continue to push the boundaries of gene editing to improve human health?

Single-nucleotide variants are the primary cause of many monogenic diseases, leading to severe conditions by disrupting protein function, gene regulation, or splicing. Traditional genome editing technologies have some significant limitations: double-strand breaks (DSBs) introduce risks of unintended mutations, and homology-directed repair (HDR) is notoriously inefficient, especially in non-dividing cells.

The Pin-point™ base editing platform provides a programmable, adaptable solution that reduces risks associated with DSBs, to help address these challenges and unlock further advancements for in vivo genetic engineering therapies.

Precision and efficiency

The Pin-point platform offers greater precision in correcting SNVs without requiring DSBs or donor DNA templates compared to traditional technologies. This innovative approach provides high efficiency and specificity, making it an ideal tool for gene therapy companies aiming to develop in vivo genetic engineering therapies. By addressing the risks associated with traditional methods, the Pin-point platform provides a safer and more reliable alternative for therapeutic applications.

Modular design for customization

One of the standout features of the Pin-point platform is its modular design, which allows for the flexible assembly of DNA binding Cas and DNA modifying deaminase components via an aptamer encoded in the guide RNA (gRNA). Gene therapy scientists can leverage this modularity to design and customize base editor configurations tailored to correct diverse pathogenic SNVs. The ability to create bespoke editor configurations means that therapeutic interventions can be precisely targeted to individual genetic mutations.

Scalable screening and predictive models

The Pin-point platform supports scalable screening methods, including arrayed and pooled screening, to comprehensively characterize novel editor configurations. These screening activities generate valuable data that feed into predictive models, continuously refining the design of future base editor configurations. For gene therapy companies, this means access to a robust pipeline of validated base editor assemblies with strong potential for preclinical development.

Optimization in cellular models

Targeted screening in cellular models accelerates the optimization of editor configurations, providing precise and efficient editing in relevant biological contexts. This process is also crucial for validating promising targets discovered from preclinical pooled screening and advancing them towards clinical applications. Gene therapy companies can benefit from the streamlined optimization and validation workflows provided by Revvity, enhancing the development of effective in vivo genetic engineering therapies with the Pin-point platform.

Commercial availability: democratizing access to innovation

While access to advanced base editing technologies can be limited due to complex intellectual property and licensing landscapes, accessing the Pin-point platform is different. Revvity offers commercial licenses for clinical development, making this powerful technology available to biotech and pharma companies ready to bring innovative therapies to patients.

This commitment to accessibility opens up exciting opportunities for both academics and gene therapy companies to integrate cutting-edge genome editing tools into their research and development efforts. By partnering with Revvity, companies can access the latest advancements in precision genome engineering and drive innovation in therapeutic interventions.

Conclusion

The Pin-point base editing platform represents a significant leap forward in the field of gene therapy. Its precision, modular design, compatibility with scalable screening methods and rapid optimization in cellular models make it a potentially powerful tool for developing in vivo gene edited therapies. Gene therapy companies looking to advance their research and create impactful therapeutic solutions should consider the Pin-point platform as a cornerstone of their genetic engineering strategy.

Check out our scientific poster to learn more.