Next Generation Gene Delivery Technologies
‘Despite the incredible advances in genome editing with CRISPR, getting this technology to the target organ remains a challenge’.
DR. NEREA ZABALETA RESEARCHER. NEXT GENERATION GENE DELIVERY TECHNOLOGIES RESEARCH GROUP
Our research team focuses on the adeno-associated viral vector (AAV) as a vehicle to bring genetic therapies to the target tissue. Particularly, we have experience in the modification of the AAV capsid for more specific and potent targeting. For this, we use advanced methodologies based on the generation of high diversity AAV capsid libraries that are screened in several in vivo and in vitro models to select capsids with optimal traits.
Our main differentiator is that our approach is disease-specific to select capsids that properly target the disease-affected tissue. In this context, inherited kidney diseases are a big focus of the laboratory.
Our emerging research group has the potential of making a great impact in the management of inherited kidney disease by providing efficacious and safe advanced genetic therapies.
Dra. Nerea Zabaleta
GROUP LEADER
| +34 948 194 700 | Ext. 81 4023 | |
| nzabaleta@unav.es | |
| Research profile |
Objectives of our research
Develop novel vectors
To develop novel vectors with improved efficacy and safety for gene delivery to different organs and tissues.
Understand mechanisms
To understand the mechanisms of viral vector transduction and replication to improve in vivo tissue targeting and manufacturing.
Designing strategies
To design in vivo gene editing approaches to treat monogenic diseases
Clinical translation
The clinical translation of novel advanced therapies for genetic kidney diseases.
The gene therapy has encountered challenged when delivering therapeutic genes to certain organs and tissues. The kidney is one of these organs, with a complex structure and function, many differentiated cell types and a tight regulation of their function. Around 600 inherited kidney diseases affecting a single gene have been identified so far, with an estimated 2% of the population suffering one of these diseases. The existing gene delivery technologies have a low efficacy of kidney targeting, and this is causing a delay in the development of efficacious therapies for inherited kidney diseases. Our research group is applying advanced techniques to develop improved vectors for kidney gene transfer.
Medical problem we are investigating
Genetic medicine has advanced in the past decades, allowing to treat genetic disorders with different strategies, such as, gene augmentation or gene editing. For examples, the discovery of CRISPR/Cas9 gene editing technologies has opened multiple possibilities towards precision medicine. However, many of these approaches require the in vivo delivery of the genetic medicine to the target tissue.
The currently used delivery vehicles show several limitations, including inefficient delivery to certain tissues, toxicity, immune system activation, limited packaging capacity y non-optimal manufacturing.
Lines of research
PI: Nerea Zabaleta
Autosomal dominant policystic kidney disease (ADPKD) is a highly prevalent disease (1:1,000) characterized by the development of renal cysts that lead to chronic kidney disease. The main goal of this project is to develop advanced therapies for the treatment of ADPKD.
Objectives:
- Development of modified adeno-associated vectors (AAV) for improved gene transfer to renal tubular cells
- Generation of in vivo gene editing startegies for the treatment of ADPKD
- Characterization of gene editing therapies in patient-derived kidney organoids
PI: Nerea Zabaleta
Schwann cells are responsible for generating the myelin that covers nerves and allows for optimal transmission of nerve impulses. Genetic errors in these cells lead to the development of diseases called Charcot-Marie-Tooth. In collaboration with Dr. Afrooz Rashnonejad at Nationwide Children´s Hospital (Columbus, Ohio), we are developing adeno-associated vectors (AAV) that can deliver therapeutic DNA to Schwann cells.
Objectives:
- Identification of key residues in the AAV capsid for the transduction of Schwann cells.
- Generation of new AAV capsids with improved Schwann cell transduction efficiency and specificity by inserting peptides into the capsid Surface.
PI: Nerea Zabaleta
PARVAX is a novel vaccine platform based on pro-inflammatory AAVs that allow the transfer of antigen-encoding genes in an optimal context for the generation of an immune response. This project aims to generate knowledge that will enable the clinical translation of this technology.
Objectives:
- To determine the mechanism of potency and durability of antigen-specific immunity after a single dose of PARVAX.
- Engineering of the capsid and the recombinant genome to achieve protective immunity at a lower PARVAX dose.
- Explore new applications of PARVAX such as the prevention of viral infections or the treatment of cancer.
Meet the research team
Scientific activity of the Next Generation Gene Delivery Technologies Research Group
Latest scientific publications
- Gene editing in liver diseases Oct 24, 2024 | Magazine: FEBS Press
- Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates Aug 2, 2024 | Magazine: Vaccines
- Efficient and Safe Therapeutic Use of Paired Cas9-Nickases for Primary Hyperoxaluria Type 1 Jan 16, 2024 | Magazine: EMBO Molecular Medicine
- Gene therapy for liver diseases - progress and challenges May 20, 2023 | Magazine: Nature Reviews Gastroenterology & Hepatology