Nicolau Lab
The Nicolau Lab aims to further the translational development of gene editing therapies for muscle disorders, with a particular emphasis on genetic mutations that require insertion of hundreds or thousands of base pairs into genomic DNA. The team's first goal is to apply novel gene editing technologies such as homology-independent targeted integration (HITI) and prime editing to correct these mutations. In addition, they aim to investigate and address the obstacles to in vivo muscle gene editing, including viral delivery mechanisms, muscle regeneration and immune responses.
Inside Nicolau Lab
Our Research
Homology-independent targeted integration (HITI)-based gene editing can be used to correct mutations in the DMD gene and restore dystrophin expression.
Most inherited myopathies present in childhood or young adulthood, and they typically lead to substantial disability and shortened life expectancy. Duchenne muscular dystrophy (DMD) is the most common of these, affecting approximately 1 in 5000 boys. Despite a number of advances in recent years, therapeutic options for DMD remain imperfect because they rely on the expression of truncated versions of the dystrophin protein. The therapeutic landscape is even more limited in other inherited muscle diseases, most of which do not have any approved therapies. Many of the genes implicated in muscle diseases are too large to package into viral vectors and thus require alternative therapeutic strategies, such as correction of the underlying mutations in genomic DNA.
Featured Publications
- Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-Label Study
- CRISPR-Cas9 Homology-Independent Targeted Integration of Exons 1-19 Restores Full-Length Dystrophin in Mice
- Automated Immunofluorescence Analysis for Sensitive and Precise Dystrophin Quantification in Muscle Biopsies
- A Molecular Diagnosis of LGMDR1 Established by RNA Sequencing
Featured Projects
- Expression of full-length dystrophin through targeted insertions into the DMD gene
- Analysis of AAV integrations into the host genome
- Immune responses and muscle turnover in neuromuscular gene editing
Join Our Team
The Nicolau Lab is always growing. If you are interested in joining our team as a student intern, clinical research coordinator, or post-doctoral fellow, please email us with a cover letter and a CV/Resume at Stefan.Nicolau@NationwideChildrens.org.
