Nonviral producer cell proteins incorporated into retroviral vector surfaces profoundly influence infectivity and in vivo half-life. We report the purification and concentration of lentiviral vectors using these surface proteins as an efficient gene transduction strategy. Biotinylation of these proteins and streptavidin paramagnetic particle concentration enhances titer 400- to 2,500-fold (to 10(9) CFU/ml for vesicular stomatitis virus G protein and 5 x 10(8) for amphotropic murine leukemia virus envelope). This method also uses newly introduced membrane proteins (B7.1 and DeltaLNGFR) directed to lentiviral surfaces, allowing up to 17,000-fold concentrations. Particle conjugation of lentivirus allows facile manipulation in vitro, resulting in the transduction of 48 to 94% of human acute myeloid leukemia blasts.
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http://dx.doi.org/10.1128/JVI.79.20.13190-13194.2005 | DOI Listing |
Blood
January 2025
Department of Pediatrics, Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA.
X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease.
View Article and Find Full Text PDFAntiviral Res
December 2024
NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Electronic address:
Emerging studies demonstrate that lipid conjugation is a vital strategy for designing peptide-based viral fusion inhibitors, and the so-called lipopeptides exhibit greatly improved antiviral activity. In the design of lipopeptides, a flexible linker between the peptide sequence and lipid molecule is generally required, mostly with a short polyethylene glycol or glycine-serine sequence. Very recently, we discovered that the helix-facilitating amino acid sequence "EAAAK" as a rigid linker is a more efficient method in the design of SARS-CoV-2 fusion inhibitory lipopeptides.
View Article and Find Full Text PDFChem Commun (Camb)
November 2024
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
Herein, we develop an L-RNA aptamer, L-Apt.T8, for recognizing HIV-1 U3-III RNA G-quadruplex, and conjugate the L-Apt.T8 with DNA antisense (L-Apt.
View Article and Find Full Text PDFCurr HIV Res
January 2025
Department of Chemistry, University of Fort Hare, Alice, South Africa.
Background: The incorporation of anti-HIV drugs into polymer to form polymer-drug conjugates has been reported to result in improved therapeutic activity. Zidovudine, an anti-HIV drug, was explored alone and in combination with known drug molecules using polyamidoaminebased carriers.
Objective: Polymer-drug conjugates incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic acid were prepared and evaluated for their potential efficacy in vitro against pseudo- HIV-1.
J Med Chem
October 2024
Department of Pharmacology & Chemical Biology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
Inherently limited by poor bioavailability, antiviral agent tenofovir (TFV) is administered to people living with HIV in prodrug form. However, current prodrugs are prematurely metabolized, compromising access to HIV-infected cells and inducing toxicity. Inspired by lipid conjugate TFV exalidex (TXL), we recently disclosed TXL analogs with potent activity and robust hepatic stability in vitro, as well as attractive oral PK profiles in vivo.
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