Page 14 - Hormel Institute Annual Report 2021-22

George Aslanidi, PhD
“Our lab develops safe and effective tools for genetic manipulation to revise what nature has planned in an effort to change the outcome to a more positive one for patients
with rare genetic diseases and cancer.”
George Aslanidi
14 | THE HORMEL INSTITUTE // Molecular Bioengineering and
Cancer Vaccine
ASSOCIATE PROFESSOR
UNIVERSITY OF MINNESOTA
We use rational molecular bioengineer- ing to develop the capsid- and expression cassette modified adeno-
associated virus (AAV) vectors. These optimized viral vectors further the possible treatment of a vast variety of rare genetic disorders and cancer. In some cases, genetic material is delivered
by the virus directly to the diseased tissues
and substitutes the dysfunctional gene. For example, Cockayne syndrome (CS) is a severe, ultra-rare autosomal recessive disease in which symptoms can include, but are not limited to premature aging, short stature, microcephaly, photosensitivity, and neurological dysfunction. Although the major underlying genetic causes of CS (mutations in the ERCC8 (CSA) or ERCC6 (CSB) genes), have been identified, there is currently no disease altering therapy available for those who suffer from this devastating disease. Another example is Cystic Fibrosis – the lack of cystic fibrosis transmembrane con- ductance regulator (CFTR) causes the improper function of lung cells, accumulation of excessive mucus, bacterial contamination and ultimately lung failure. In other cases, a tumor-specific
antigen carried by these novel AAV vectors is injected into an in vivo model of melanoma or prostate cancer using standard needle vacci- nation procedures. As a result, local antigen presenting cells (APC) uploaded with the AAV-delivered tumor antigen either directly or by a cross-presentation pathway activate both a cytotoxic CD8+ T-cells and a humoral response against the tumor.
Current research projects
Our current research is taking advantage of the AAV accumulation in EVs to develop a novel “stealth” approach for AAV delivery, subsequent efficient gene expression, and vector re- administration strategy. Recent advances in EV characterization make it possible to have quantitative assessments of the properties of EV-AAV formulations as potent gene delivery vehicles. To this end, we will apply these state- of-the-science characterization techniques to study the accumulation of AAVs in EVs and
the properties of these formulations – vesicle concentration, size distribution, morphology, protein biomarkers, cargo – that yield optimal protection of the associated/encapsulated AAVs