Related Experiment Video
Updated: Aug 25, 2026
Radial Mobility and Cytotoxic Function of Retroviral Replicating Vector Transduced, Non-adherent Alloresponsive T Lymphocytes
Published on: February 11, 2015
Biodistribution of the RD114/mammalian type D retrovirus receptor, RDR
Bronwyn J Green1, C Soon Lee, John E J Rasko
1Gene Therapy Research, Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Sydney Cancer Centre, Locked Bag 6, Newtown, NSW 2042, Australia.
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.
Insights
This study directly analyzed RDR expression, a key receptor for gene therapy vectors, across various human tissues. Findings reveal RDR is present in many tissues but shows significant individual variability, impacting gene therapy strategies.
Area of Science:
- Molecular Biology
- Gene Therapy
- Immunology
Background:
- Viral receptor expression on target cells limits therapeutic gene transfer.
- Previous receptor analysis relied on indirect methods due to a lack of specific antibodies.
Purpose of the Study:
- To directly analyze the expression of RDR (a neutral amino acid transporter and receptor for RD114-pseudotyped vectors) in various human tissues using specific antibodies.
- To assess the distribution and variability of RDR expression relevant to gene therapy applications.
Main Methods:
- Utilized anti-RDR antiserum for direct histochemical and flow cytometric analysis.
- Investigated RDR expression in normal tissues, immature cells, germ cells, and hematopoietic cell subsets.
Main Results:
- RDR is expressed in normal tissues like colon, testis, ovary, bone marrow, and skeletal muscle.
- High RDR expression was observed on immature cells in squamous epithelia (skin, cervix, etc.).
- RDR expression varied significantly among individuals within hematopoietic lineages, with myeloid and monocytic cells showing the highest expression.
Conclusions:
- Biodistribution studies of viral receptors like RDR are crucial for optimizing gene transfer protocols.
- Inter-individual variation in RDR expression suggests the need for personalized gene therapy approaches.
