Pin-point™ Base Editing Platform

FAQs

• How customizable is the Pin-point base editing platform for specific targets?

  Every target is different. That’s why the Pin-point system was designed with flexibility at its heart. Unlike traditional base editors that rely on fixed, Cas-fused constructs, the Pin-point platform uses a modular aptamer-recruitment system, decoupling the Cas targeting machinery from the deaminase payload. This architecture allows for precise customization of editing conditions based on your target site, cell type, and delivery method.

  What can be tuned?

  • Choice of deaminase – A growing toolbox of deaminases allows for different editing windows and sequence preferences.
  • Recruitment strategy – Aptamer-based recruitment offers the ability to recruit different deaminases to different locations of the genome in a single reaction.
  • Titration of editing components – Delivery of each component (Cas, deaminase, gRNA) can be balanced to favor efficient on-target editing with reduced off-target risk.
  • Cell-type-specific optimization – Expression levels, editing kinetics, and repair environments vary across cell types. The Pin-point system can be fine-tuned accordingly.

• What if I have a tough or sensitive target?

  Whether you’re working with difficult PAM contexts, narrow editing windows, or targets prone to off-target liabilities, we’re here to help. Our team collaborates with partners to identify the right configuration and support testing in relevant systems, either through technical evaluation or co-development.

  We meet you where you are. The Pin-point platform isn’t a one-size-fits-all solution, it’s a flexible toolkit to help you solve your specific gene editing challenge, with the data, support, and licensing model to back it up.

• Can I multiplex edits using the Pin-point base editing platform?

  Yes, and you should. In many current editing workflows, especially for iPSC-derived or T cell therapies, each edit is done sequentially:

  • One edit per transfection
  • Multiple rounds of culture and selection
  • Compounding stress, culture-acquired abnormalities, and genomic instability

  With the Pin-point base editing platform, you can make multiple edits in a single round, without double-strand breaks (DSBs) and without overloading the cell.

  Here’s how:

  • Cas-deaminase decoupling allows a single Cas to perform multiple functions independently and specifically
  • Aptamer-recruitment enables multiple deaminases to be directed simultaneously to different loci
  • Reduced exposure time and titratable elements minimize off-target activity, even with multiplexed editing

  Get in touch with our team to discuss how multiplex editing could be applied in your system.

• What are the applications of multiplex editing?

  As gene and cell therapy programs grow more sophisticated, the need to modify multiple targets simultaneously has become central to improving efficacy, safety, and manufacturability. Multiplex base editing enables complex engineering strategies that would be impractical or risky with traditional nuclease methods:

  • Multiple knockouts to deactivate redundant or suppressive genes
  • Knockout + knock-in to inactivate a locus and reprogram it with a functional sequence or exogenous payload
  • Polygenic SNV correction for multigenic diseases or immune evasion profiles
  • SNV correction + knock-in to restore function and deliver a payload simultaneously
  • Dual ABE and CBE editing for precision tuning across adenine and cytosine targets in one go

  Why does this matter? It means less time in culture, a lower risk of unwanted mutations, and a more development-friendly path to clinical-grade cells.

  If you want to see how multiplex editing could be applied in your system, let’s talk - get in touch with our team today.

• What makes base editing safer than traditional CRISPR-Cas9 approaches?

  One word: precision. For therapeutic applications, DNA safety is non-negotiable. Traditional CRISPR-Cas9 and nuclease-based approaches work by inducing double-strand breaks (DSBs) in the genome. While effective for gene knockout, this strategy comes with known risks:

  • Genotoxic stress from repeated or persistent DNA damage
  • Structural variants and large deletions at or near the cut site
  • Chromosomal rearrangements, especially in stem cells or long-term engrafting cells

  Regulators are paying attention. Recent FDA guidance for cell-based gene therapy calls for deeper characterization of editing-related genomic changes and minimizing unintended modifications wherever possible.

  With the Pin-point base editing platform, we avoid DSBs from the start. Instead of breaking the DNA, we make single-nucleotide changes at the base level with high efficiency and low disruption.

  This matters because cleaner genomes lower the risk for oncogenic transformation. Shorter culture time for complex engineering means fewer opportunities for culture-acquired mutations, and reduced DSBs also reduced stress on sensitive or long-lived cell types

  Furthermore, almost any CRISPR knockout used in a therapeutic setting can be achieved via base editing. From premature stop codons to splice site disruption, we can knock out genes without collateral damage.

  If you're still relying on nucleases for clinical editing, it may be time to re-evaluate your risk profile. Contact our team to find out how we can help.

• Is base editing a replacement for all gene editing applications?

  Not every application is a perfect fit for base editing, but you might be surprised by how much base editors like the Pin-point platform can do!

  Some applications like large structural rearrangements may still require nuclease-based tools or other strategies, at this point in technology development. But for the vast majority of therapeutic editing applications, base editing with the Pin-point platform offers a safer, smarter path forward.

  From simple gene knockouts to complex, multiplexed edits (including knockout and knock-in at the same time), base editing has evolved into a next-generation alternative to traditional CRISPR-Cas9 with real-world advantages:

  • Single-gene knockouts via premature stop codons or splice disruption
  • Knockout and knock-in workflows using targeted base changes plus HDR for non-viral targeted insertion
  • Single or polygenic SNV correction for precision repair of disease-causing mutations
  • Multiplex editing with lower risk of genotoxic stress or culture-acquired abnormalities
  • And all while avoiding double-strand breaks

  What sets the Pin-point platform apart is not just the chemistry, it’s the control, tunability, and enzyme flexibility that makes these applications safer and more feasible across sensitive cell types like T cells, iPSCs, and HSPCs.

  In a field where DNA damage is no longer considered benign, DSB-free base editing isn't just a technical upgrade. It's an evolving regulatory and therapeutic imperative.

• How can I get started with the Pin-point base editing platform?

  Whether you're early in evaluation or preparing for program integration, there are multiple ways to begin working with the Pin-point platform:

  • Technical evaluations – Conducted under MTA with support from our scientific team to assess performance in your specific cell type, target, or workflow
  • Pilot studies – May be performed by your team or contracted to Revvity’s base editing experts, depending on your in-house capabilities
  • Licensing – Flexible agreements tailored to your field of use and stage of development

  We also offer off-the-shelf RUO reagents with select configurations of the Pin-point platform available as mRNA reagents for researchers looking to quickly test or prototype in-house.

  And for turnkey support, Revvity’s preclinical services team provides a range of expert offerings using the Pin-point platform, including:

  • Cell line engineering
  • Pooled and tiled screening

  Whether you're biotech, pharma, or an academic group tackling rare disease, we’re here to help you get started, thoughtfully and efficiently.

  Contact our team to discuss your needs today!