| First Author | Sava V | Year | 2020 |
| Journal | Nanomedicine | Volume | 24 |
| Pages | 102119 | PubMed ID | 31666200 |
| Mgi Jnum | J:298517 | Mgi Id | MGI:6480207 |
| Doi | 10.1016/j.nano.2019.102119 | Citation | Sava V, et al. (2020) Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington's disease gene expression following intranasal administration. Nanomedicine 24:102119 |
| abstractText | Therapies to lower gene expression in brain disease currently require chronic administration into the cerebrospinal fluid (CSF) by intrathecal infusions or direct intracerebral injections. Though well-tolerated in the short-term, this approach is not tenable for a life-time of administration. Nose-to-brain delivery of enriched chitosan-based nanoparticles loaded with anti-HTT siRNA was studied in a transgenic YAC128 mouse model of Huntington's Disease (HD). A series of chitosan-based nanoparticle (NP) formulations encapsulating anti-HTT small interfering RNA (siRNA) was designed to protect the payload from degradation "en route" to the target. Factors to improve production of effective nanocarriers of anti-HTT siRNA were identified and tested in a YAC128 mouse model of Huntington's disease. Four formulations of nanocarriers were identified to be effective in lowering HTT mRNA expression by at least 50%. Intranasal administration of nanoparticles carrying siRNA is a promising therapeutic alternative for safe and effective lowering of mutant HTT expression. |
