Transduction of lymphoid progenitors with retroviral or lentiviral vectors is a powerful experimental strategy to tease out the role of a gene or pathway in T cell development via gain-of-function or loss-of-function strategies. Here we discuss different approaches to use this powerful technology, and present some protocols that we use to transduce murine HSCs, thymocytes, and lymphoid cell lines with these viral vectors.
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http://dx.doi.org/10.1007/978-1-4939-2809-5_8 | DOI Listing |
Cells
November 2024
Great Ormond Street Institute of Child Health, University College London, London WC1E 1EH, UK.
Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases haemophilia A and B are exemplifying the success of liver-directed viral gene therapy. In parallel, additional gene therapy strategies are rapidly emerging to overcome some inherent AAV limitations, such as the non-persistence of the episomal transgene in the rapidly growing liver and immune response. Viral integrating vectors such as in vivo lentiviral gene therapy and non-viral vectors such as lipid nanoparticles encapsulating mRNA (LNP-mRNA) are rapidly being developed, currently at the preclinical and clinical stages, respectively.
View Article and Find Full Text PDFJ Genet Eng Biotechnol
December 2024
Department of Hematology, Amsterdam UMC, Location VU University Medical Center, Cancer Center Amsterdam, Room CCA3.38, De Boelelaan 1117, Amsterdam 1081 HV, the Netherlands.
The past decades have illustrated the power of T-cell engineering in the development of new and successful cell therapies, such as chimeric antigen receptor (CAR) T-cells. Despite clinical success in hematological malignancies, it also becomes increasingly clear that additional T-cell engineering will be required to improve efficacy and safety and expand the application to solid tumors. Engineering is most often achieved by viral delivery of transgenes, however, viral vector capacity limitations make efficient and reproducible generation of multi transgene expressing T-cell therapeutics technically challenging.
View Article and Find Full Text PDFJ Vis Exp
November 2024
Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine; Institute of Immunology and Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine;
T helper cells that produce IL-17A, known as Th17 cells, play a critical role in immune defense and are implicated in autoimmune disorders. CD4 T cells can be stimulated with antigens and well-defined cytokine cocktails in vitro to mimic Th17 cell differentiation in vivo. Research has been conducted extensively on the Th17 differentiation regulation mechanisms using the in vitro Th17 polarization assay.
View Article and Find Full Text PDFNeurosci Lett
January 2025
Department of Anatomy and Neurobiology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0709, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, P.O. Box 980613, Richmond, VA 23298-0613, USA; Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, P.O. Box 980059, Richmond, VA 23298-0059, USA. Electronic address:
Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased.
View Article and Find Full Text PDFJ Integr Neurosci
October 2024
Department of Neurology, Headache Center, The First Hospital of Shanxi Medical University, 030001 Taiyuan, Shanxi, China.
Background: The aim of this study was to investigate the possible molecular mechanisms underlying cerebral small vessel disease caused by a missense mutation in the high-temperature serine peptidase A1 gene, (NM_002775.4, Exon4, c.905G>A, p.
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