Enhanced siRNA Delivery Using a Novel Peptide
The given technology involves the use of a PTD-DRBD (peptide transduction domain-dsRNA binding protein) fusion peptide. DRBD binds siRNAs with high avidity independent of its sequence and allows PTD-mediated cellular uptake. PTD-DRBD mediated siRNA delivery occurs by a specialized process of macropinocytosis that prevents siRNA escape into the cytoplasm. UCSD researchers have tested this approach in 20+ cell types including human Embryonic Stem Cells, HUVECs, fibroblasts, keratinocytes and hematopoietic lineages and remarkably, siRNA responses were induced in the entire cell population in all 20 cell types in a rapid and non-cytotoxic fashion. In addition, PTD-DRBD siRNA delivery approach has been tested with great success in mouse models.
Patent Number: US20120101045A1
Application Number: US13319326A
Inventor: Dowdy, Steven F. | Eguchi, Akiko
Priority Date: 7 May 2009
Priority Number: US20120101045A1
Application Date: 7 Nov 2011
Publication Date: 26 Apr 2012
IPC Current: A61K003817 | A61P003500 | C07K001400 | C07K001447 | C12N0005071
US Class: 5140193 | 435375 | 5140209 | 530300 | 530322 | 530358
Assignee Applicant: The Regents of the University of California
Title: TRANSDUCIBLE DELIVERY OF NUCLEIC ACIDS USING MODIFIED dsRNA BINDING DOMAINS
Usefulness: TRANSDUCIBLE DELIVERY OF NUCLEIC ACIDS USING MODIFIED dsRNA BINDING DOMAINS
Summary: For introducing an anionically charged nucleic acid molecule (preferably double stranded (ds)RNA) into cell; and for inhibiting expression of target nucleic acid in cell or subject, where target nucleic acid is nucleic acid that promotes cancerous phenotype (claimed) for treating cancer. Also useful for inducing RNA interference (RNAi) responses for manipulation of phenotypes for discovery research, and for treating viral diseases.
Novelty: New substantially purified polypeptide to treat e.g. cancer has specific amino acid length, and at least two histidine substitutions compared to specific nucleic acid binding polypeptides e.g. histone, protamine, or protein kinase R
诊断/治疗
癌症/肿瘤
9260493
Applications 1) siRNA delivery reagent Related Materials Eguchi et al., Efficient siRNA delivery into primary cells by a peptide transduction domain–dsRNA binding domain fusion protein. Nature Biotechnology 27, 567 - 571 (2009) Tech ID/UC Case 19213/2009-213-0 Related Cases 2009-213-0
2) RNAi basic research
3) Target screening and siRNA therapeutics
Eguchi and Dowdy, siRNA delivery using peptide transduction domains. Trends in Pharmacological Sciences, Volume 30, Issue 7, 341-345 (2009)
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