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Enhanced siRNA Delivery Using a Novel Peptide

Detailed Technology Description

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.

Supplementary Information

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

Industry

Disease Diagnostic/Treatment

Sub Category

Cancer/Tumor

Application No.

9260493

Others

Applications

1) siRNA delivery reagent
2) RNAi basic research
3) Target screening and siRNA therapeutics

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)
Eguchi and Dowdy, siRNA delivery using peptide transduction domains. Trends in Pharmacological Sciences, Volume 30, Issue 7, 341-345 (2009)

Tech ID/UC Case

19213/2009-213-0

Related Cases

2009-213-0

*Abstract

siRNA delivery into cells can often times be challenging especially in certain cells such as primary cells and hematopoietic cell lineages. Lipofection reagents which are routinely used for siRNA transfection can result in varying degrees of cytotoxicity. Researchers at UCSD have developed a novel peptide that exhibits a dramatic increase in siRNA delivery and in addition over-comes problems associated with cytotoxicity.

*IP Issue Date

Feb 16, 2016

*Principal Investigator

Name: Steven Dowdy

Department:

Name: Akiko Eguchi

Department:

Country/Region

USA