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

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Gene Therapy for Monogenic Encephalopathies. Research Group. Cima

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.

Genetic scissors to treat kidney diseases

Desarrollo de Tecnologías de Transferencia de Genes. Cima Universidad de Navarra

The research group has launched the RENALGENE project, focused on developing gene therapies for genetic kidney diseases. It consists of applying gene editing strategies using CRISPR machinery, a kind of “genetic scissors” that would allow the mutation present in patients to be corrected and the effects of the disease to be reversed.

The project has received €1.5 million in funding from the European Union through the European Research Council's ERC Starting Grant awarded to Dr. Nerea Zabaleta in the 2025 call for proposals.

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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.