Biodistribution of the RD114/mammalian type D retrovirus receptor, RDR

Background The limited expression of viral receptors on target cells is a recognized barrier to therapeutic gene transfer. Previous analysis of receptor expression has been performed using indirect methods due to a lack of receptor-specific antibodies. Methods In this report we have used anti-RDR antiserum to provide direct histochemical and flow cytometric analysis of the expression of RDR, which is the cognate receptor for RD114-pseudotyped vectors as well as being a neutral amino acid transporter. Results RDR was present on a range of normal tissues with relevance to gene therapy including: colon, testis, ovary, bone marrow and skeletal muscle. It was also highly expressed on immature cells present in the squamous epithelia of skin, cervix, nasal mucosa, bronchus and tonsil. Of relevance to possible germline gene transfer, we demonstrated a lack of RDR expression on male or female germ cells. RDR expression on mature hemopoietic cell subsets showed up to 5-fold variability between individuals within each lineage - with some individuals expressing low levels of RDR across all blood lineages. Both myeloid and monocytic lineages contained the highest fraction of cells expressing RDR, whereas lymphoid lineages showed the lowest. Coexpression of CD34 and RDR ranged from 2.04 to 0.44% in G-CSF-mobilized peripheral blood samples. Conclusions As a means to optimize gene transfer protocols, biodistribution studies such as these are fundamental to enable targeting of the virus receptor most abundantly expressed on relevant populations. The inter-individual variation of receptor expression seen here also raises the possible requirement for tailor-made gene therapy protocols. Copyright (C) 2004 John Wiley Sons, Ltd.