The growing societal burden of neurodegenerative disease as the average age of the world population increases, as well our inability to develop effective clinical treatments, poses a critical problem. Although many therapeutic factors can effectively treat animal models of Alzheimer's disease, progress has been slowed by the challenge of successfully delivering therapies to the aged human brain. My graduate work focused on the development of adeno-associated virus (AAV) vectors for gene delivery to the nervous system. As a postdoctoral fellow, I have applied my graduate training in the rational design and neurobiological function of AAV vectors to develop novel gene therapies for the treatment of AD. In transitioning to the field of aging research, I aim to harness my expertise with AAV vectors to enhance our ability to control and target therapeutic gene delivery to the aged brain.
1. Vandenberghe LH, Bell P, Maguire AM, Cearley CN, Xiao R, Calcedo R, Wang L, Castle MJ, Maguire A, Grant R, Wolfe JH, Wilson JM & Bennett J (2011). Dosage thresholds for clinical translation of AAV2 and AAV8 photoreceptor targeted gene therapies in a non-human primate model. Sci Transl Med 3 (88): 88ra54. PMID: 21697530.
2. Castle MJ, Perlson E, Holzbaur EL & Wolfe JH (2014). Long-distance Axonal Transport of AAV9 is Driven by Dynein and Kinesin-2 and is Trafficked in a Highly Motile Rab7-positive Compartment. Mol Ther 22: 554-66. PMID: 24100640.
3. Castle MJ, Gershenson ZT, Giles AR, Holzbaur EL & Wolfe JH (2014). AAV Serotypes 1, 8, and 9 Share Conserved Mechanisms for Anterograde and Retrograde Axonal Transport. Hum Gene Ther 25: 705-29. PMID: 24694006.
4. Castle MJ, Cheng Y, Asokan A & Tuszynski MH (2018). Physical Positioning Dramatically Enhances Brain Transduction After Intrahecal AAV9 Infusion. Sci Adv 4(11): eaau9859. PMID: 30443600.
1. Castle MJ, Turunen HT, Vandenberghe LH & Wolfe JH (2016). Controlling AAV tropism in the nervous system with natural and engineered capsids. In: Gene Therapy for Neurological Disorders (Manfredsson FP, ed). Meth Mol Biol 1382: 133-49. New York: Humana Press. PMID: 26611584