Research Terms
Evelyn F. & William L. McKnight Brain Institute of the University of Florida
Director |
Todd Golde |
Phone | (352) 273-8501 |
Website | http://www.mbi.ufl.edu/ |
Mission | The mission of the Evelyn F. & William L. McKnight Brain Institute of the University of Florida is to understand how normal CNS development and function contribute to higher cognitive functions, including lifelong learning and memory, via complex interactive neural circuitries that produce all of our incredible human behaviors. Focusing on the ability to remember and learn throughout life, treatment of movement disorders, brain cancer and stroke, our dedicated scientists and clinical investigators rely on state-of-the-art facilities, resources and creativity that are required for the discovery of powerful new protocols to treat all neurological disorders that have the potential to impair quality of life. Our dedication to this mission will continue to lead to advances in knowledge of the normal, compromised, protected and repaired CNS. |
This large-scale production of rAAV employs embryonated avian eggs to stably package and produce adeno associated viral (AAV) vectors. A powerful research and clinical tool, AAVs deliver genetic material to specific cells and provide in vivo long-term gene expression. Available manufacturing processes are expensive and unable to meet the demand for large quantities of high quality AAVs needed for clinical trials. Though common in vaccine production, the gene therapy industry has not previously attempted to use embryonated avian eggs to package and propagate recombinant AAV.
Researchers at the University of Florida developed a technique to produce AAVs in larger quantities by using embryonated avian eggs as the host vehicles. This technique is cost-effective, compatible with process regulations for current Good Manufacturing Practice, adaptable to existing machinery and methods of vaccines, and more scalable than other viral vector production processes.
Cost-effective, large-scale production of recombinant AAV using embryonated avian eggs
This technique to produce AAV vectors within embryonated avian eggs involves transfection of a single plasmid that comprises all genes necessary for efficient packaging. AAV vector growth in embryonated avian eggs can provide large scale manufacturing capacity similar to what vaccine industries achieve. The technique works with any AAV serotype and transgene packages for creating rAAV particles, and it is compatible with process regulations required for manufacturing clinical compounds.
These decoy protein receptors can be used to treat neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s and Parkinson’s, affect more than 6 million people in the United States. Over time and with age, the body’s natural protein growth can start to develop abnormalities or become more susceptible to pathogens, affecting physical and cognitive functions. Toll-like receptors (TLRs) are cell surface proteins that act as sensors detecting infections or other foreign microbial protein. Once an infection is detected, toll-like receptors activate the innate and adaptive responses of the immune system for protection. Available toll-like receptor inhibitors can potentially trigger unexpected, detrimental side effects by weakening the body’s innate immune system. Researchers at the University of Florida have developed these soluble toll-like receptor decoys to detect and treat neurodegenerative diseases. The decoy protein receptors better synergize with the body’s natural defense capacity, creating a treatment for proteinopathy diseases without compromising the body’s innate immune system. Especially promising are decoy receptors based on soluble toll-like receptor 5, which by binding amyloid ß protein aggregates, can have major impact on amyloid accumulation, which is thought to trigger Alzheimer’s disease.
Decoy protein receptors detect and treat neurodegenerative diseases caused by protein abnormalities or pathogens
Toll-like receptors are essential in activating the antimicrobial inflammatory responses of the immune system. Toll-like receptors have special leucine-rich ligand binding ectodomain on the surface that can recognize pathogen/disease associated molecular patterns. University of Florida researchers have developed these specially designed soluble polypeptides using the same surface binding sites as the natural toll-like receptors to invoke the body’s immune response to specific diseases. When the ligands of toll-like receptors bind with different pathogen-associated molecular patterns, local cells start transcription of infection and inflammatory mediators. Administration of an effective amount of a soluble polypeptide directly or peripherally to the brain can treat a wide range of neurodegenerative proteinopathy diseases, including Alzheimer’s disease, Parkinson’s disease, synucleinopathy, or tauopathy.