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  • A novel therapeutic molecule against HTLV-1 infection targeting provirus.

A novel therapeutic molecule against HTLV-1 infection targeting provirus.

Leukemia (2013-02-16)
A Tanaka, S Takeda, R Kariya, K Matsuda, E Urano, S Okada, J Komano
ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) in humans, establishes a life-long latent infection. Current therapies are not very effective against HTLV-1-associated disorders. A novel therapeutic approach may help to combat HTLV-1 infection. A molecular therapy that targets the proviral genome is favorable because the therapeutic effect occurs specifically in HTLV-1-infected cells, regardless of whether they express viral genes. In this proof-of-concept study, we developed a therapeutic molecule based on zinc finger nuclease (ZFN) to achieve this goal. We designed a ZFN that specifically recognized conserved region of HTLV-1 long terminal repeat (LTR) and introduced it into various HTLV-1-positive human T-cell lines, including HTLV-1-transformed and ATL-derived cell lines. The ZFN disrupted the promoter function of HTLV-1 LTR and specifically killed HTLV-1-infected cells. We also showed a potential approach of this therapeutic molecule to remove the proviral genome from HTLV-1-infected cells, something that has not been possible before. The therapeutic effect of ZFN was confirmed in an in vivo model of ATL. This strategy may form the basis of a therapy that can eradicate HTLV-1 infection. Similar approaches can be used to target other malignancy-associated viruses.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
CompoZr Custom Zinc Finger Nuclease (ZFN), ZFN plasmid only
Sigma-Aldrich
CompoZr® Custom Zinc Finger Nuclease (ZFN), ZFN plasmid and mRNA
Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution