REVIEW_ARTICLE
HIV-Derived Lentiviral Vectors: Current Progress toward Gene Therapy and DNA Vaccination
Lentiviral vectors are promising gene delivery tools capable of transducing a variety of dividing and non-dividing cells, including pluripotent stem cells which are refractory for transduction by murine retroviruses. Although there is a growing debate on the safety of lentiviral vectors for gene transfer, in particular for those derived from human immunodeficiency viruses, type one (HIV-1) and type two (HIV-2), these vectors are envisioned to possess several advantages. Importantly, they can be utilized not only for transducing specific target cells or for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS), but also in a pseudotype recombinant form can be used for different target cells including neurological and cancer cells. For HIV-2, the most com-pelling advantages are: (i) its reduced ability to recombine with resident HIV-1 genome (ii) its ability to induce in recipients antibodies which can be distinguished from host immune response to HIV-1 (iii) HIV-2 is apparently less pathogenic and (iv) may downregulate HIV-1 expression. This review will summarize new developments on HIV-1 vectors, while focusing on alternate strategies toward developing HIV-2-based vectors.
http://ibj.pasteur.ac.ir/article-1-854-en.pdf
2015-11-23
95
103
HIV-Lentiviral Vectors
Gene Therapy
DNA Vaccination
Gene Delivery
M. Reza
Sadaie
1
AUTHOR
Suresh K.
Arya
2
AUTHOR
ORIGINAL_ARTICLE
Evaluation of (5R,6R)-5-Bromo-6-Ethoxy-5-Ethyl-5,6-Dihydro-2\'- Deoxyuridine as a Brain-Targeted Prodrug of 5-Ethyl-2\'- Deoxyuridine
(+)-Trans-(5R,6R)-5-bromo-6-ethoxy-5-ethyl-5,6-dihydro-2'-deoxyuridine [(5R,6R)-BEEDU], a potential brain-targeted prodrug of 5-ethyl-2'-deoxyuridine (EDU), was synthesized by the regiospecific addition of BrOEt to the 5,6-olefinic bond of EDU. (5R,6R)-BEEDU is more lipophilic (log P = 0.04) than EDU (log P = -1.09). In vitro incubation of (5R,6R)-BEEDU with rat whole blood and brain homogenate resulted in a 53% and 16% conversion, respectively, to EDU. In contrast, (5R,6R)-BEEDU was not converted to EDU upon incubation with glutathione (GSH) at 37°C for 36 hours. After i.v. injection into rats, (5R,6R)-BEEDU was rapidly converted to EDU, which was then further metabolized like EDU. However, (5R,6R)-BEEDU provided a substantially higher Ryncentration of EDU in blood, relative to that when EDU was injected. A biodistribution study of [4- C]-(5R,6R)-BEEDU in Balb/c mice showed that (5R,6R)-BEEDU provided significantly higher (P < 0.05) radirctivityievels in brain samples at 8, 18 and 30 min post injection than observfid after injection of [4- C]-EDU. The higher repioactivity levels in liver samples after injection of [4- C]-(5R,6R)-BEEDU, relative to those after [4- C]-EDU, indicates that the 5,6-dihydro derivative undergoes a higher hepatic extraition than EDU. Clearance of radioactivity from blood qv' excretion into urine, after injection of [4 C]EDU, was much faster than that after injection of [4- C]-(5R,6R)-BEEDU.
http://ibj.pasteur.ac.ir/article-1-862-en.pdf
1998-07-15
105
113
5-Ethyl-2-deoxyuridine
Dihydro prodrugs
Herpes Simplex Virus
Brain-targeted
Majid
Cheraghali
1
AUTHOR
Rakesh
Kumar
2
AUTHOR
Kevin W.
Morin
3
AUTHOR
Edward E.
Knaus
4
AUTHOR
Leonard I.
Wiebe
5
AUTHOR
ORIGINAL_ARTICLE
Enzyme-Linked Immunosorbent Assay of Progesterone in Serum Using Penicillinase as Label
An enzyme-linked immunosorbent assay (ELISA) for progesterone measurement in serum or plasma samples using penicillinase as label enzyme is reported. A C3 and C11 derivatives of progesterone were prepared and conjugated to bovin serum albumin (BSA). Polyclonal antibody against these two immunogens were prepared in New Zealand white rabbits. Purified Ig fractions of antibodies were immobilized onto the wells of microtiter plates. Progesterone 3-(O-carboxymethyl ) oxime was linked to penicillinase and used as tracer (enzyme-conjugate). The standard assay completed within three hours had a low limit of detection, from 5 pg/well (50 pg/ml) covering up to 1 ng/well (10 ng/ml). For the first time in this assay the color development in case of penicillinase as enzyme label was measured in the wells directly. Recoveries were measured to be within the range of 95-98%. Percent Coefficient of variations (CV%) obtained between and within runs of several assays were 3% and 7% respectively. When compared between values of progesterone measured by radioimmunoassay (RIA) and present ELISA method, a correlation value of r = 0.9 was obtained. Freeze-dried progesterone-enzyme conjugate was found stable for at least three months at 4° C without using any other preservative.
http://ibj.pasteur.ac.ir/article-1-863-en.pdf
1998-07-15
115
122
Progesterone
ELISA
Penicillinase
Behrokh
Farahmand
1
AUTHOR
Mohamad Javad
Rasaee
2
AUTHOR
Naser
Maleknia
3
AUTHOR
Mohamad
Malekaneh
4
AUTHOR
ORIGINAL_ARTICLE
DNA-Repair Capacity in Down\'s Syndrome
Down's syndrome (DS) is the most common chromosomal abnormality in human. Subjects with DS are known to be peridisposed to develop leukemia. The molecular basis of the association between DS and leukemia is unknown. The unscheduled DNA synthesis (UDS) test measure the ability of DNA-repair in mammalian cells after excision of a stretch of DNA containing the region of damage induced by chemical or physical agents. To get further insight into the cause(s) of leukemia in DS, the induction of UDS, in human peripheral blood lymphocytes was determined using hydroquinone and ethidium bromide, as DNA-damaging agents. Peripheral lymphocytes were obtained from 14 patients (7 males, 7 females) and 14 healthy sex- and age-matched normal subjects. The mean of UDS observed in control lymphocytes when treated with hydroquinone and ethidium bromide were 1.69 + 0.65, and 1.10 + 0.29, respectively, and corresponding values for DS lymphocytes were 1.11 + 0.40 and 0.92 + 0.26, respectively. Our results revealed that the lymphocytes of DS patients, showed a decrease in the UDS level. These data suggest that the low capacity of DNA-repair in conjunction with hypersensitivity of DNA and chromosomes of DS patients after treatment with mutagens may be relevant to the high incidence of leukemia in DS patients.
http://ibj.pasteur.ac.ir/article-1-864-en.pdf
1998-07-15
123
127
Down's syndrome
Trisomy 21
Unscheduled DNA synthesis
UDS
DNA-repair
Iraj
Saadat
1
AUTHOR
Abdol-Amir
Allameh
2
AUTHOR
Mostafa
Saadat
3
AUTHOR
ORIGINAL_ARTICLE
Block of 5-HT2 Receptors Enhances Hippocampal Long-Term Potentiation
The effect of endogenous serotonin on long-term potentiation (LTP) in region CAI was studied by blocking 5-HT2 receptors with ketanserin in rat hippocampal slices. Such a block significantly en-hanced long-term potentiation of the CAI population spike induced by high frequency stimulation of the schaffer collateral/ commissural pathway. This implies that serotonin acts on 5-HT2 receptors in CAI to repress long-term potentiation.
http://ibj.pasteur.ac.ir/article-1-865-en.pdf
1998-07-15
129
131
Long-term potentiation
Synaptic plasticity
Serotonin
Hippocampus
Nasser
Naghdi
1
AUTHOR
Neveill
Goodwin
2
AUTHOR
Susan
Pocket
3
AUTHOR
SHORT_COMMUNICATION
Regional Assignment of Ptpre Encoding Protein Tyrosine Phosphataes ε to Mouse Chromosome 7F3
Protein tyrosine phosphatases (PTPases) regulate the tyrosine phosphorylation of target proteins involved in several biological activities including cell proliferation and transformation. Protein tyrosine phosphatase E (PTPE) contains duplicated PTPase-like domains and a short extracellular region. Using the fluorescence in situ hybridization method, the gene encoding PTPE (locus symbol Ptpre) was mapped to mouse chromosome 7F3. These results indicate that there is a conserved syntenic group between human chromosome 10q26 and mouse chromosome 7F3.
http://ibj.pasteur.ac.ir/article-1-866-en.pdf
2015-11-23
133
135
PTPε
Mouse
Gene mapping
Chromosome 7
Mostafa
Saadat
1
AUTHOR