Cocal vesiculovirus envelope pseudotyped retroviral vectors

Abstract

Provided herein are Cocal vesiculovirus envelope pseudotyped retroviral vectors that exhibit high titers, broad species and cell-type tropism, and improved serum stability. Disclosed Cocal vesiculovirus envelope pseudotyped retroviral vectors may be suitably employed for gene therapy applications and, in particular, for the ex vivo and in vivo delivery of a gene of interest to a wide variety of target cells.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application No. 61 / 175,376, filed May 4, 2009, and which provisional patent application is incorporated by reference in its entirety herein.GOVERNMENT SPONSORED RESEARCH OR DEVELOPMENT[0002]This disclosure was made, in part, in the course of research sponsored by the National Institute of Health, grant numbers HL36444, DK47754, HL074162, DK07786, DK56465, HL53750, AI061839, and AI063959. The U.S. government has certain rights in this disclosure.SEQUENCE LISTING[0003]The present application includes a Sequence Listing in electronic format as a txt file titled “Sequence_Listing—04May10,” which was created on May 4, 2010 and which has a size of 21 kilobytes (KB). The contents of txt file “Sequence_Listing—04May10” are incorporated by reference herein.BACKGROUND OF THE DISCLOSURE[0004]1. Technical Field of the Disclosure[0005]The present disclosure relates, generally, to the field...

AI Technical Summary

Benefits of technology

[0014]The present invention addresses these and other related needs by providing, inter alia, Cocal vesiculovirus envelope pseudotyped retroviral vector particles that may be suitably employed for gene transfer applications including gene therapy and vaccines, and, in particular, for the ex vivo and in vivo delivery of a gene of interest to a wide variety of target cells. The Cocal vesiculovirus envelope pseudotyped retroviral vector particles disclosed herein exhibit high titers, broad species and cell-type tropism, and improved serum stability.

Problems solved by technology

There are, however, some disadvantages to using VSV-G to pseudotype retroviral vectors.

Toxicity is associated with the constitutive expression of VSV-G, which has made generation of stable packaging cell lines difficult (Ory et al., Proc. Natl. Acad. Sci. U.S.A.

The titers reported for RD114 / TR pseudotyped lentiviral vectors have, however, generally been lower than those obtained with VSV-G, which may limit their utility for clinical gene therapy applications.

Images