Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington’s disease gene expression following intranasal administration.

Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington’s disease gene expression following intranasal administration.

Publication date: Oct 27, 2019

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) were 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.

, Sava, Fihurka, O., Khvorova, A., and Sanchez-Ramos, J. Enriched chitosan nanoparticles loaded with siRNA are effective in lowering Huntington’s disease gene expression following intranasal administration. 06742. 2019 Nanomedicine.

Concepts Keywords
Brain SiRNA
Cerebrospinal Fluid Gene therapy
Chitosan Nasal administration
Huntington Nanomedicine
Intranasal Administration Nanocarriers
Intrathecal Chitosan
MRNA Small interfering RNA
Mutant Clinical medicine
Nanocarriers Molecular biology
Nanomedicine RNA interference
Nanoparticle Branches of biology
Nanoparticles Disease
NP Gene therapy
SiRNA
Transgenic

Semantics

Type Source Name
gene UNIPROT SLC6A4
gene UNIPROT HTT
gene UNIPROT CSF2
disease DOID brain disease
disease MESH brain disease
pathway BSID Gene Expression

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