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>Joy Zuchero

About The Speaker

Joy Zuchero

Director and Principal Scientist at Denali Therapeutics

Joy Zuchero

I am currently Director and Principal Scientist at Denali Therapeutics. My group focuses on development and characterization of BBB delivery platforms and their unique biological interaction with therapeutic targets in vivo using cutting edge technologies. I have 15 years of experience in this area of BBB research, first at Genentech (2009-2015), before joining Denali in 2015 to initiate and lead BBB-crossing platform efforts from the ground up.

At Denali, I lead multiple cross-functional project teams focused on understanding and developing neurodegeneration therapeutic targets utilizing our BBB delivery platforms. I have also led multiple external collaborations, both with other biotechnology companies as well as with academic groups. My research has led to numerous peer-reviewed papers and patents on BBB platform technology.

The Transport Vehicle: Engineering the Fc and Utilizing the Brain Vasculature to Deliver CNS Therapeutics

The inability of large molecule therapeutics to cross the blood-brain barrier has remained a major obstacle for the treatment of neurological disorders. Numerous strategies have aimed to increase brain exposure of biotherapeutics; approaches which utilize transport across the BBB via the rich capillary network are expected to significantly increase exposure in the brain and additionally result in broad distribution throughout the brain.

Our approach utilizes the Transport Vehicle (TV), which binds to receptors, such as the transferrin receptor (TfR) and CD98hc, present on the BBB via modifications to the Fc region of an IgG. The TV-targeted receptors are expressed on brain vascular endothelial cells and enable transport of bound molecules across the BBB to reach target cells in the brain parenchyma. The molecular architecture of the TV platform is highly modular and enables the delivery of numerous types of biotherapeutics, including antibodies, enzymes, proteins, oligonucleotides, etc. with the potential to meaningfully increase drug concentrations in the CNS for the treatment of neurological disorders.

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