Happy to share that my postdoctoral work is now out in
@ScienceMagazine. We show that the RNA-programmable bridge recombinase ISCro4 can insert, delete, or invert multi-kilobase DNA fragments at defined genomic sites in human cells.
Study link:
science.org/doi/10.1126/scie…
CRISPR-Cas has transformed genome editing, but many diseases involve diverse patient-specific mutations within the same gene. A mutation-agnostic alternative is to insert a healthy gene copy at a defined genomic locus, but gene-sized, site-specific insertions remain a major challenge.
Main findings of our work:
(1) ISCro4 is highly active in human cells and can be delivered by plasmid or all-RNA formats
(2) Proof-of-concept programmable multi-kb insertions, deletions, and inversions
(3) Structural insights into the basis of enhanced ISCro4 activity
(4) Specificity and off-target characterisation
(5) A framework to support future development and adoption of bridge recombinases
The work was made possible through a close collaboration between the Jinek Lab,
@schwanklab, and
@jcornlab. I am deeply grateful to all of my co-authors for the team spirit, hard work, and dedication that went into this publication:
@talasandris, Javier Fernández Carrera,
@nicopmat, Lilly van de Venn, Charles Yeh,
@p_kulcsar,
@marquark,
@YanikWeber,
@SaskiaGerecke, Isabelle Harvey-Seutcheu, Dominic Mailänder,
@MorPfl, and
@ChrisChanez89. Special thanks to my supervisor, Prof. Martin Jinek, for his outstanding mentorship, and to Prof. Gerald Schwank and Prof. Jacob Corn for their generous support throughout. Finally, I would like to thank everyone in the Jinek lab for creating a supportive work environment, and
@EMBO for funding my postdoctoral work.
In parallel, independent work led by
@ntperry13,
@SKonermann and
@pdhsu also reported ISCro4 activity in human cells, reinforcing the robustness and momentum of this direction.
Please reach out if you would like to test the system or discuss potential applications. Relevant plasmids are now available via
@Addgene.