Gene editing could fix genetic errors and create healthy skin grafts to help heal DEB wounds.
 Bearded man with glasses wearing a lab coat and smiling at the camera
Dr Sergio López-Manzaneda works at CIEMAT in Spain on this gene editing project to correct genetic changes that cause DEB. This project aims to use new CRISPR/Cas9 technology to repair the broken parts of the collagen-7 gene (COL7A1) in skin cells grown in the laboratory. This genetic ‘patching’ involves cutting out part of the gene and inserting a ‘patch’ with the working sequence. If successful, the genetically patched skin cells could be used in the future to create grafts of healthy skin to heal DEB wounds.


About our funding:

Research leader Dr Sergio López-Manzaneda
Institution Fundación Jiménez Díaz, CIEMAT, Spain
Type of EB DEB
Patient involvement No
Funding amount £15,000
Project length 1 year
Start date TBC 2024
DEBRA internal ID GR000042

Latest progress summary:

Due 2025.


About our researchers:

Lead researcher:

Dr Sergio López-Manzaneda is a researcher at CIEMAT with a strong background in genome editing.


Dr Fernando Larcher is associate professor of biochemistry at Universidad Carlos III de Madrid and Head of Division at CIEMAT (Epithelial Biomedicine Division).

Alex Bassons Bascuñana is a PhD student in the Epithelial Biomedicine Group of the Biomedical Innovation Unit at CIEMAT.


Dr Paula Rio is an internationally recognised expert in gene editing and gene therapy of inherited hematopoietic diseases, from basic science to clinical trials.


Why this research is important:

This non-viral gene editing approach looks for a low-cost and universal strategy to generate a library of tools capable to address every known mutation... In future pre-clinical studies, gene “patched” edited keratinocytes and fibroblasts from patients will be used to generate bioengineered skin equivalents.

Dr Sergio López-Manzaneda


Researcher’s abstract:

Grant title: Non-viral genome editing patching of COL7A1.

In this project, we propose a genome editing strategy focused on the treatment not of just one point mutation but groups of neighboring mutations causing RDEB, by repairing full exons harboring them. This “genetic-patching” is based on the natural Homologous Recombination (HR) DNA repair mechanism facilitated by the CRISPR/Cas9 system. The “patches” represent small (300-400 base pairs) double stranded HDR donor DNA templates that would be designed from gene sequences enough to cover few contiguous exons, in this case, corresponding to the COL7A1 gene encoding type VII collagen. Our aim is to characterize (efficacy, safety) and to standardize the use of these technology with the idea of having specific patches readily available to tackle individual groups of mutations. The non-viral technology proposed for ex vivo RDEB patient cell treatment will facilitate its translation to the clinic at low cost. 

One of the most promising therapeutic approaches for EB is genome editing using CRISPR/Cas9 technologies. During the last 7 years our laboratory has been actively working in this field providing strong proof-of-concept data aiming at translating its results to the clinic. While we are in the verge of clinical application with one of these approaches that obtained an Orphan Drug designation by the European Medicines Agency (EU/3/20/2253), we continue seeking for more efficient, safer and clinically relevant genome editing strategies.

In this project, we propose to test an innovative gene editing approach that does not require the use of viral vectors (all material is introduced by a single electroporation). The goal is to use these “genetic patches” to correct mutated regions after having cut this genetic region with CRISPR/Cas9 technology. We have designed four different “patches”, this means, dsDNA donor templates specifically modified in their ends by a proprietary technology of our provider (Integrated DNA technologies, IDT) to favour HDR. These templates contain two exons and their surroundings (73 and 80, two “patches” each) and four different cut points (two for Exon 73 and two for exon 80). This templates  (around 300-400 bp) also cover the neighbour exons.

We aim to evaluate the extent of the repair within the “patches” which would allow us to address groups of mutations or, if the system works well enough, to fully correct the exons within the “patches”. We believe that this novel, no viral, personalized gene editing strategy could be easily translated to the clinic with a significant low economical cost.


Researcher’s progress update:

Due 2025.


Back to contents

Image credit: National Human Genome Research Institute.