Dimostrazione di cura positiva della fibrosi epatica con cambio del gene difettoso direttamente con somministrazione diretta nel soggetto cavia. (mouse with human PiZ allele)
Intellia Demonstrates Consecutive In Vivo Genome Editing in Alpha-1 Antitrypsin Deficiency Mouse Model
Intellia’s oral presentation highlights its alpha-1 antitrypsin deficiency (AATD) study showing that consecutive dosing of two distinct lipid nanoparticle (LNP) formulations, in adult mice, achieves two targeted genome editing events, resulting in knocking out the faulty gene and restoring therapeutic levels of normal alpha-1 antitrypsin protein (hAAT). Intellia’s approach for AATD uses a modular hybrid delivery system combining a non-viral LNP which encapsulates CRISPR/Cas9 with an adeno-associated virus (AAV) carrying donor DNA template. Compared to traditional viral-based delivery of gene editing components, Intellia’s LNP delivery system can overcome the inherent limitations of immunogenicity to facilitate multiple in vivo gene editing events.
In a mouse model harboring the human PiZ allele, the most severe genetic defect in AATD patients, Intellia first reduced expression of the defective protein using gene knockout. Three weeks following the PiZ allele knockout, Intellia inserted the normal human alpha-1 antitrypsin gene, resulting in stable (throughout 12 weeks of observation), therapeutically relevant circulating protein levels. In the study, a sustained reduction of the circulating PiZ protein levels of >98% was observed for over 15 weeks. This is the first in vivo demonstration of a non-viral delivery platform, enabling a consecutive dosing approach for achieving multiple genome edits in the same tissue of the same animal. Intellia’s oral presentation, titled “In Vivo Gene Knockout Followed by Targeted Gene Insertion Results in Simultaneous Reduced Mutant Protein Levels and Durable Transgene Expression,” will be given by Anthony Forget, Ph.D., on October 25, 2019. This presentation will be available on Intellia’s website at
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in seguito nel sito si fa riferimento a collaborazioni con ospedali per la cura di altre malattie sempre con tecniche CRISPR based