Page 16 - Hormel Report 2021

George Aslanidi, Ph.D.
“Our lab develops a 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
16 | THE HORMEL INSTITUTE // Molecular Bioengineering and
Cancer Vaccine
SECTION LEADER / ASSOCIATE PROFESSOR
UNIVERSITY OF MINNESOTA
We use rational molecular bioengineer- ing to develop the capsid- and expres- sion cassette modified adeno-associ-
ated virus (AAV) vectors. These optimized viral vectors further used for possible treatment of vast verity of rare genetic disorders and cancer. In some case, genetic material delivered by virus directly to the diseased tissues and substitute dysfunctional gene. For example, Cockayne syndrome (CS) is a severe, ultra-rare autoso-
mal 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 exam- ple is Cystic Fibrosis – lack of cystic fibrosis transmembrane conductance regulator (CFTR) causing improper function of lung cell, accumu- lation of excessive mucus, bacterial contamina- tion and ultimately lung failure. In other cases, tumor specific antigen carried by these novel
AAV vectors are injected into in vivo model of melanoma or prostate cancer using standard needle vaccination 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 we are taking advantage of recently described 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 possible 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 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 from immune surveillance. We also will