Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.

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Specific human chromosomal elements enhance the performance of episomal gene-transfer vectors. S/MAR-based episomal vector pEPI-eGFP transfects CD34 + haematopoietic cells, but only transiently.To address this issue we reinforced (1) transgene transcription by replacing the CMV promoter driving eGFP with the EF1/HTLV or SFFV promoters to produce vectors pEPI-EF1/HTLV and pEPI-SFFV, respectively; and (2) plasmid replication by inserting the replication-Initiation Region (IR) from the β-globin locus into vector pEPI-SFFV to produce vector pEP-IR. All vectors supported stable transfections in K562 cells. Transfections of CD34 + cells from peripheral blood of healthy donors reached 30% efficiency. Upon evaluation of CD34 + /eGFP + cells in colony-forming cell (CFC) assays, vector pEP-IR showed superior performance after 14 days, by fluorescent microscopy: 100% eGFP + -colonies against 0% for pEPI-eGFP, 56.9% for pEPI-SFFV and 49.8% for pEPI-EF1/HTLV; 50% more plasmid copies per cell and 3-fold eGFP expression compared to the latter two constructs, by quantitative (q)PCR and RT-qPCR, respectively. Importantly, the establishment rate in CFC assays was 15% for pEP-IR against 5.5% for pEPI-SFFV and 5% for pEPI-EF1/HTLV. Vector pEP-IR shows extremely low delivery rate but supports eGFP expression in thalassaemic mouse haematopoietic progenitor cells. The IR is a novel human control element for improved episomal gene transfer into progenitor cells.The design and use of extrachromosomal vectors, suitable for efficient and stable transfection of haematopoietic progenitor cells, is an important goal for the gene therapy of haemoglobinopathies. The development of extrachromosomal vectors has mainly been driven by the need to address the safety issue of gene therapy vectors, in particular, the problem of insertional mutagenesis 1 , and involves vectors such as self-replicating stable episomes 2 , pFARs-plasmids free of antibiotic resistance markers 3 , and minicircle DNA plasmid derivatives lacking a bacterial backbone 4 . The presence of the scaffold/matrix attachment region (S/MAR) also confers long-term mitotic stability to integration-deficient lentiviral, episomal vectors 5,6 ; however, that of the truncated S/MAR does not improve episomal retention 7 .Key issues in the development of episomal vectors are currently the establishment in the host nucleus 8,9 , the transgene expression 10,11 and the delivery in progenitor cells 10 . The prototype episomal vector pEPI-1 2 does not code for any viral protein, and it contains the S/MAR from the 5′ end of the human β -interferon gene 2 , an element that facilitates the vector's nuclear retention.The S/MARs are AT rich chromosomal elements that play a role in chromatin boundary formation 12 and bind to SAF-A protein 13 , mediating the tethering of pEPI-1 plasmid to the nuclear matrix. A prerequisite for

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