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5 ways to boost the success of your gene editing project

Published 18 June 2025 by Sean Butler

Why the right gene editing tools make all the difference

Gene editing technologies like CRISPR-Cas9 and base editors have revolutionised biomedical research, with applications spanning functional genomics, disease modeling, and the development of precision therapeutics. Yet even the most advanced editing systems can fall short without the right tools - precision, reproducibility, and efficiency still hinge on the quality of the reagents and assays you use.

From optimising new editing systems to troubleshooting guide RNAs, the reagents you choose can dramatically impact experimental outcomes. Below are five evidence-backed ways to enhance the success of your gene editing projects.

1. Prioritise high-quality recombinant proteins

At the core of any gene editing platform are the editing enzymes - Cas9, Cas12, Cas13, and others. Enzyme quality is not trivial: suboptimal folding, instability, or low activity can significantly compromise editing efficiency and introduce variability. Studies have shown that protein purity and conformational integrity directly influence cleavage activity and target specificity (Koblan et al., 2018; Pickar-Oliver & Gersbach, 2019).

Choosing proteins with high activity and batch-to-batch consistency ensures fewer failed experiments and more reproducible data - especially important for scalable or translational applications.

2. Measure editing activity early

Waiting until phenotypic readouts to assess editing success increases the risk of discovering issues too late. Instead, using early-stage, quantitative assays to measure nuclease activity, indel formation, or off-target effects provides critical feedback when optimisation is still feasible.

In vitro cleavage assays and cell-based reporter systems can help screen gRNA performance or compare delivery strategies before committing to long-term studies. This aligns with best practices outlined in gene editing QC workflows (Tsai et al., 2015).

3. Validate function beyond the cut

Detecting a successful edit at the DNA level is just the beginning. To confirm biological relevance, it's essential to assess downstream effects - such as protein expression, signaling pathway modulation, or changes in cellular phenotype. Functional validation ensures that the intended outcome has been achieved, and helps identify unintended consequences, such as compensatory effects or off-target disruptions.

Reporter assays and pathway analysis tools can streamline this step, providing a window into gene function and edit fidelity (Senturk et al., 2017).

4. Match proteins to your application

Not all reagents are equally suited to every application. Whether you're working on CRISPR-mediated gene knockouts, base editing, RNA modification, or synthetic biology, using proteins that are optimised for specific formats and delivery methods (e.g., RNPs, mRNA, or viral vectors) can significantly improve outcomes.

Custom-formulated enzymes - designed with high purity and structural integrity - are especially important for sensitive or emerging applications like prime editing and epitranscriptomic regulation (Anzalone et al., 2020).

5. Minimise complexity with ready-to-use solutions

Even the most experienced labs encounter setbacks due to poorly characterised reagents or inconsistent assay kits. Using validated, pre-optimised components can dramatically reduce troubleshooting time and allow researchers to focus on discovery rather than technical hiccups.

Efficient workflows often depend on simplifying upstream steps - especially in fast-paced or high-throughput settings. Wherever possible, choose tools that are QC-tested, protocol-friendly, and backed by responsive technical support.

Final thoughts: Your gene editing success starts with the right tools

If you're looking to increase the efficiency, accuracy and reproducibility of your gene editing work, investing in high-quality reagents and assays is essential.
BPS Bioscience offers the gold standard in CRISPR-related biochemical and cell-based assays, while KACTUS delivers high-activity proteins and enzymes backed by advanced design and batch consistency.

Together, they provide a powerful, integrated solution - supporting every step of your gene editing journey from initial design to final validation.

References:

1. Koblan, L.W., Doman, J.L., Wilson, C. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nature Biotechnology 36, 843–846 (2018). https://doi.org/10.1038/nbt.4172

2. Pickar-Oliver, A., Gersbach, C.A. The next generation of CRISPR–Cas technologies and applications. Nature Reviews Molecular Cell Biology 20, 490–507 (2019). https://doi.org/10.1038/s41580-019-0131-5

3. Tsai, S.Q., Zheng, Z., Nguyen, N.T. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nature Biotechnology 33, 187–197 (2015). https://doi.org/10.1038/nbt.3117

4. Senturk, S., Shirole, N.H., Nowak, D.G. et al. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization. Nature Communications 8, 14370 (2017). https://doi.org/10.1038/ncomms14370

5. Anzalone, A.V., Randolph, P.B., Davis, J.R. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019). https://doi.org/10.1038/s41586-019-1711-4