Dataset Information

MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression.

ABSTRACT: Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA was primarily via site-specific cleavage of the transgene mRNA, generating specific 5' and 3' mRNA fragments. Our findings promise to facilitate the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other applications.

SUBMITTER: Xie J

PROVIDER: S-EPMC3048189 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression.

Xie Jun J Xie Qing Q Zhang Hongwei H Ameres Stefan L SL Hung Jui-Hung JH Su Qin Q He Ran R Mu Xin X Seher Ahmed Seemin S Park Soyeon S Kato Hiroki H Li Chengjian C Mueller Christian C Mello Craig C CC Weng Zhiping Z Flotte Terence R TR Zamore Phillip D PD Gao Guangping G

Molecular therapy : the journal of the American Society of Gene Therapy 20101221 3

Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the ...[more]

PMID: 21179009

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Dataset Information

MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression.

Publications

MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression.

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