Traumatic brain injury (TBI), commonly caused by motor vehicle injury and falls in the young and elderly, afflicts nearly 1.7 million people in the United States each year. n addition to being a leading cause of death in children and young adults, TBI is also a major cause of permanent disability in the United States. There are currently no curative treatments for TBI, and the main course of action is to minimize secondary damage that results from changes in blood pressure, brain swelling, or intracranial pressure that is triggered by the initia injury. The overall goal of this project is to first develop a well-tolerated means of transferring genes to neural progenitor cells in the brain and then to use this technology to direct cortical neurogenesis after injury. We propose to use focused ultrasound to enhance non-viral gene transfer to neural progenitor cells in the brain mediated by a targeted polymer delivery vector, thus enabling the delivery of genes encoding fibroblast growth factor-2 and neurogenin2, proteins shown to enhance neurogenesis and direct neuron differentiation, respectively. We will evaluate in an animal model of TBI whether induced migration and increased neuronal integration can lead to functional improvement through a combination of histology, cognitive evaluations, and motor assessments. .
Despite the enormous physical, emotional and financial toll resulting from the over 1.7 million cases of traumatic brain injury that occur in the United States per year, there is currently no cure available for either the primary or secondary damage that result from these insults. The main goal of this application is to develop a clinically-translatable approach to enhance neurogenesis in the brain. We expect that the technology developed from the proposed work will present a significant advance toward repair of lost neurons in the brain.
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| Yen, Albert; Cheng, Yilong; Sylvestre, Meilyn et al. (2018) Serum Nuclease Susceptibility of mRNA Cargo in Condensed Polyplexes. Mol Pharm 15:2268-2276 |
| Lee, Daniel C; Lamm, Robert J; Prossnitz, Alex N et al. (2018) Dual Polymerizations: Untapped Potential for Biomaterials. Adv Healthc Mater :e1800861 |
| Olden, Brynn R; Cheng, Yilong; Yu, Jonathan L et al. (2018) Cationic polymers for non-viral gene delivery to human T cells. J Control Release 282:140-147 |
| Feldmann, Daniel P; Cheng, Yilong; Kandil, Rima et al. (2018) In vitro and in vivo delivery of siRNA via VIPER polymer system to lung cells. J Control Release 276:50-58 |
| Rosenberg, Alexander B; Roco, Charles M; Muscat, Richard A et al. (2018) Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science 360:176-182 |
| Comedy, Yolanda L; Gilbert, Juan E; Pun, Suzie H (2017) INVENTION IS NOT AN OPTION. Technol Innov 18:267-274 |
| Cheng, Yilong; Sellers, Drew L; Tan, James-Kevin Y et al. (2017) Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers. Biomaterials 127:89-96 |
| Cheng, Yilong; Wei, Hua; Tan, James-Kevin Y et al. (2016) Nano-Sized Sunflower Polycations As Effective Gene Transfer Vehicles. Small 12:2750-8 |
| Cheng, Yilong; Yumul, Roma C; Pun, Suzie H (2016) Virus-Inspired Polymer for Efficient In?Vitro and In?Vivo Gene Delivery. Angew Chem Int Ed Engl 55:12013-7 |
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