细胞功能测定

Epithelial cell polarity mediates many essential biological functions and perturbation of the apical/basolateral divide is a hallmark of epithelial to mesenchymal transition in carcinoma. Therefore, correct targeting of proteins to the apical and basolateral surfaces is es ...

Plasma membrane (PM) proteins are of particular interest to cell biologists because of their role in transducing information from the external environment to the cell interior, and because of their potential as therapeutic targets. The hydrophobicity and large size of these proteins r ...

Modulation of intracellular signaling pathways or receptor expression in natural killer (NK) cells by genetic manipulation is an attractive possibility in studies of NK cell specificity and function. Moreover, feasible applications of these genetic manipulations in the conte ...

Dendritic cells (DCs) play a key role in the orchestration of immune reactions. Manipulation of DC function through genetic manipulation for vaccine development provides a multitude of applications for active immunotherapy of cancer and chronic infections. Several laboratori ...

Adult bone marrow stem cell is an ideal target for gene therapy of genetic diseases, selected malignant diseases, and AIDS. The in vivo approach of lentivirus vector (LV)-mediated stem cell gene transfer by intrafemoral (IF) injection can take full advantage of any source of stem cells residing in ...

The thymus provides a specialized environment allowing the differentiation of T lymphocytes from bone marrow-derived progenitor cells. We and others have demonstrated that gene transfer into distinct thymocyte populations can be obtained, both in vivo and ex vivo, using lentiviral ...

Successful retroviral gene transfer into hematopoietic cells has been demonstrated in a number of small and large animal models and clinical trials. However, severe adverse events related to insertional muta-genesis in a recent clinical trial for X-linked severe combined immunode ...

RNA interference (RNAi) is an evolutionarily conserved sequence-specific post-transcriptional gene silencing mechanism triggered by double-stranded RNA (dsRNA) that results either in degradation of homologues mRNAs or inhibition of mRNA translation. The effector mole ...

Today the treatment of inherited diseases holds a major field in gene therapy, and γ -retroviral vectors are often the preferred tool for stable introduction of the therapeutic gene(s) into the host cell genome. In many cases, the newly introduced gene has to be constitutively expressed, since en ...

Retroviral vectors based on murine leukemia viruses (MuLV) have been used in clinical investigations for over a decade. Alternative retroviruses, most notably vectors based on HIV-1 and other lentiviruses, are now entering into clinical trials. Although vectors are designed to be repl ...

This chapter will review the design and execution of release testing requirements for retroviral vectors and gene-modified cells consistent with ensuring the success of the clinical trial on the basis of current US regulatory requirements. It is the ethical and legal responsibility of t ...

Human gene transfer with gammaretroviral, murine leukemia virus (MLV) based vectors has been shown to effectively insert and express transgene sequences at a level of therapeutic benefit. However, there are numerous reports of disruption of the normal cellular processes caused by the v ...

The hematopoietic stem cells (HSCs) constitute an ideal target for the gene therapy of inherited diseases affecting the hematopoietic system. HSCs, however, constitute a very rare population of progenitor cells, most of which are out of cycle in normal bone marrow. To facilitate their trans ...

Properly collected and stored human specimens offer the unique opportunity to study human diseases at the molecular level in the real in vivo situation. The intention of this chapter is, first, to raise the awareness for important points, which have to be clarified before human tissue samples are ...

The mouse is the most commonly used experimental animal, and a wide range of tumor types can arise in their hematopoietic system. Therefore, for research scientists and graduate students working in the field of experimental hematology, immunology, and cancer research, there is an urgent need ...

The ideal way to assess hematopoietic stem cells is to observe their growth in the endogenous microen-vironment where they would receive the appropriate signals. With colonies of inbred mice, it is possible to myeloablate recipients and transplant hematopoietic cells from genetica ...

Large animal models have played a crucial role in the development of gene therapy protocols. A significant advantage of large animal models over rodent models includes the ability to more easily translate protocols developed in large animals to humans. For gene therapy applications, non ...

In order to restore or to introduce a gene function integrating viral vector systems are used to genetically modify hematopoietic stem cells. The occurrence of immortalized cell clones after transduction in vitro (Blood 106:3932–3939, 2005) and clonal dominance as well as leukemia in pre ...

Identification of retroviral vector insertion sites in single, dominating cell clones has become an important tool for the investigation of cellular signalling pathways involved in clonal expansion and malignant transformation. Also, recent severe adverse events in clinical ...

Identification, monitoring, and analysis of genetically modified cells in the peripheral blood are an important component of the clinical follow-up of patients treated by hematopoietic cell gene therapy. Analysis of gene-marked peripheral blood cells provides crucial inform ...