Improving the gene editing toolbox Collection – Contribution Highlights
Published in Microbiology
About this Collection
Genome Biology is calling for submissions to a Collection on improving the gene editing toolbox. Technologies, including base editing or prime editing, enable users to install targeted gene modifications via single base substitutions or nearly any short sequence edits, respectively, CRISPRa and CRISPRi can regulate gene expression, various emerging technologies are being explored for exon- or kilobase-scale sequence edits, and the use of AAVs offers potential for studying effects of perturbations in vivo in mammalians. As computational approaches improve, larger-scale CRISPR screens paired with high-dimensional read-outs present the potential to map gene interactions with enhanced accuracy. These breakthroughs are reshaping biotechnology, driving progress in medicine, agriculture, and synthetic biology.
Contribution highlights
CRISPR technology holds therapeutic potential, with Casgevy, the world’s first CRISPR gene editing therapy being a relatively well-known example. Adeno-associated viruses (AAVs) have become a prevalent tool for in vivo delivery, but classical Cas9 and Cas12 proteins are generally considered too large to fit into a single AAV. Xin et. al. consider TnpB, an ancestor of the CRISPR-Cas9 and Cas12 nuclease, that is more compact than Cas12 and Cas9 nucleases. In their work, they categorize four TnpBs and identify an optimal miniature nuclease for future use. These compact and efficient genome editors expand our current toolkit and for potential therapeutic applications.
Minimizing unwanted off-target effects remains a challenge for developing effective CRISPR-based nucleases. Kakhki et. al. compare genome-wide off-target effects of available and novel dCas9-based epigenome editors to provide insight into factors influencing the delicate balance between potency and specificity for nuclease design. They find that all tested epimodifiers effectively induce DNA methylation and this deposition occurs rapidly, with CRISPRoff emerging as the most effect epimodifier for depositing and maintaining on-target locus methylation for up to 30 days post-transfection, likely due to its inclusion of the KRAB domain. Importantly, the study also reveals that off-target effects can arise from gRNA-independent activity and even non-targeting control guides, highlighting previously underappreciated challenges in epigenome-editing experiments. While current technologies are promising, improved off-target activity is of strong interest and this work helps inform future construct design and gRNA strategies for advancing the utility of DNA methylation editors in research and therapeutic applications.
Designing genome editing experiments with EditABLE
Technologies for broadening the range of editing possibilities are being published frequently, but this ever-changing landscape makes it challenging for researchers to ensure they are using the most optimal methods for their specific research question. Maxim et. al. develop EditABLE, a centralized resource to combine this information and guide RNA design into a single online tool, applying their EditABLE algorithm to mutation data from the Mayo Clinic Autosomal Dominant Polycystic Kidney Disease Mutation Database to identify the percentage of patients carrying mutations correctable via base or prime editing. By combining functionalities across multiple editing systems including prime and base editing, EditABLE offers a single-platform gateway tool for the genome editing community. EditABLE is available at https://editable-app.stanford.edu/.
Who is involved?
Guest Editors:
- Benjamin Kleinstiver, Massachusetts General Hospital & Harvard Medical School, USA
- Luca Pinello, Massachusetts General Hospital, Harvard Medical School, Broad Institute, USA
- Lan-Qin Xia, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, China
- Hao Yin, Wuhan University, China
- Yong Zhang, Southwest University, China
In-House Editor:
- Claudia Feng, Genome Biology, USA
How can I learn more about this Collection?
Visit the Collection page to read these and other submissions.
Genome Biology continues to welcome submissions until 23rd June 2026. Authors requiring more time to submit can contact the Managing Editor, Chess Law: chess.law@springernature.com
As part of this Collection-specific initiative, researchers may apply for 3 APC waivers and discounts by contacting Chess Law (chess.law@springernature.com), ideally at the time of submission or shortly thereafter. The available waivers and discounts are limited and will be requested on a first-come, first-served basis, so early submissions are encouraged. Approved waivers aren't a guarantee of publication, and the manuscripts will undergo normal peer review.
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Genome Biology
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