Izabella C. Jaramillo
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Izabella C. Jaramillo has a total of 3 co-authors. Here are the top co-authors by number of shared publications:
- Geoffrey D. Keeler
Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine
1 shared publication - Primrose Tanachaiwiwat
University of Florida, USA
1 shared publication - Zoe C. Nabakowski
Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida, College of Medicine, Gainesville, FL 32611, USA
1 shared publication
Latest Publications
- Open Access
A Rationally Designed AAV9-DM Capsid with Minimal Liver Tropism
Adeno-associated viral vectors (AAV) are the leading gene therapy in the clinic. AAV9 has been of particular interest due to its wide tropism for multiple tissue types as well as being able to cross the blood-brain barrier and transduce central nervous system tissues. However, effectively and safely targeting extrahepatic tissue following the systemic administration of AAV9 remains a challenge due to high rates of liver transduction and liver toxicity. Thus, a crucial first step in developing a safe AAV9-based vector is to reduce liver targeting. Here we utilized rational design techniques to make five point mutations in the AAV9 capsid. In doing so, we developed a novel AAV9 variant, AAV9-DM, that is characterized by reduced liver tropism as compared to AAV9 and other liver de-targeted AAV9 mutants. We show that AAV9-DM is effective at transducing cells in vivo, resulting in robust transgene expression over a 9-week period. Importantly, the AAV9-DM capsid maintains the ability to transduce non-hepatic tissues with a biodistribution similar to AAV9. This new mutant represents a novel AAV capsid that may be the basis for developing safer therapeutics to target extrahepatic tissue while reducing adverse side effects related to liver transduction.
Open AccessA Rationally Designed AAV9-DM Capsid with Minimal Liver Tropism
Adeno-associated viral vectors (AAV) are the leading gene therapy in the clinic. AAV9 has been of particular interest due to its wide tropism for multiple tissue types as well as being able to cross the blood-brain barrier and transduce central nervous system tissues. However, effectively and safely targeting extrahepatic tissue following the systemic administration of AAV9 remains a challenge due to high rates of liver transduction and liver toxicity. Thus, a crucial first step in developing a safe AAV9-based vector is to reduce liver targeting. Here we utilized rational design techniques to make five point mutations in the AAV9 capsid. In doing so, we developed a novel AAV9 variant, AAV9-DM, that is characterized by reduced liver tropism as compared to AAV9 and other liver de-targeted AAV9 mutants. We show that AAV9-DM is effective at transducing cells in vivo, resulting in robust transgene expression over a 9-week period. Importantly, the AAV9-DM capsid maintains the ability to transduce non-hepatic tissues with a biodistribution similar to AAV9. This new mutant represents a novel AAV capsid that may be the basis for developing safer therapeutics to target extrahepatic tissue while reducing adverse side effects related to liver transduction.