Adeno-associated viruses (AAV) are utilized as gene switch vectors within the therapy of monogenic issues. A variant, rationally engineered based mostly on pure AAV2 isolates, designated AAV-True Sort (AAV-TT), is extremely neurotropic in comparison with wild sort AAV2 in vivo, and vectors based mostly on it, are presently being evaluated for central nervous system functions.
AAV-TT differs from AAV2 by 14 amino acids, together with R585S and R588T, two residues beforehand proven to be important for heparan sulfate binding of AAV2. The capsid constructions of AAV-TT and AAV2 visualized by cryo-electron microscopy at 3.
Four and three.zero Å decision, respectively, highlighted structural perturbations at particular amino acid variations. Differential scanning fluorimetry (DSF) carried out at totally different pH situations demonstrated that the melting temperature (Tm) of AAV2 was persistently ∼5°C decrease than AAV-TT, however each confirmed maximal stability at pH 5.5, akin to the pH within the late endosome, proposed required for VP1u externalization to facilitate endosomal escape.
Reintroduction of arginines at positions 585 and 588 in AAV-TT precipitated a discount in Tm, demonstrating that the shortage of primary amino acids at these positions are related to capsid stability. These outcomes present structural and thermal annotation of AAV2/AAV-TT residue variations, that account for divergent cell binding, transduction, antigenic reactivity, and transduction of permissive tissues between the 2 viruses.
Particularly, these knowledge point out that AAV-TT might not make the most of a glycan receptor mediated pathway to enter cells and should have decrease antigenic properties as in comparison with AAV2.
Increased Transduction Effectivity of AAV5 to Neural Stem Cells and Immature Neurons in Gerbil Dentate Gyrus In comparison with AAV2 and rh10
The security and excessive effectivity of adeno-associated virus (AAV) vectors has facilitated their vast scale use to ship therapeutic genes for experimental and scientific functions in illnesses affecting the central nervous system (CNS). AAV1, 2, 5, 8, 9, and rh10 are essentially the most generally used serotypes for CNS functions.
Most AAVs are identified to transduce genes predominantly into neurons. Nonetheless, the exact tropism of AAVs within the dentate gyrus (DG), the area the place persistent neurogenesis happens within the grownup mind, just isn’t absolutely understood.
We stereotaxically injected 1.5 × 1010 viral genomes of AAV2, 5, or rh10 carrying inexperienced fluorescent protein (GFP) into the fitting aspect of gerbil hippocampus, and carried out immunofluorescent evaluation utilizing differentiation stage-specific markers one week after injection.
We discovered that AAV5 confirmed a considerably bigger variety of double constructive cells for GFP and Sox2 within the DG, in comparison with the AAV2 and rh10 teams. However, AAVrh10 offered a considerably bigger variety of double constructive cells for GFP and NeuN within the DG, in comparison with AAV2 and AAV5.
Our findings indicated that AAV5 confirmed excessive transduction effectivity to neural stem cells and precursor cells, whereas AAVrh10 confirmed a lot greater effectivity to mature neurons within the DG.
Native magnetic supply of recombinant adeno-associated virus AAV2(quad Y-F) mediated brain-derived neurotrophic issue gene remedy restores listening to after noise damage
Reasonable noise publicity might trigger acute lack of cochlear synapses with out affecting the cochlear hair cells and listening to threshold; thus, it stays “hidden” to plain scientific exams. This cochlear synaptopathy is likely one of the primary pathologies of noise-induced listening to loss (NIHL).
There is no such thing as a efficient therapy for NIHL, primarily due to the shortage of a correct drug supply approach. We hypothesized that native magnetic supply of gene remedy into the internal ear may very well be helpful for NIHL.
On this research, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno related virus vector (AAV2(quad Y-F)) to ship brain-derived neurotrophic issue (BDNF)-gene remedy into the rat internal ear through minimally invasive magnetic focusing on.
We discovered that the magnetic focusing on successfully accumulates and distributes SPION tagged AAV2(quad Y-F)-BDNF vector into the internal ear. We additionally discovered that AAV2(quad Y-F) effectively transfects cochlear hair cells and enhances BDNF gene expression.
Enhanced BDNF gene expression considerably recovers noise-induced BDNF gene downregulation, ABR wave I amplitude discount, and synapse loss. These outcomes recommend that magnetic focusing on of AAV2(quad Y-F)-mediated BDNF gene remedy might reverse cochlear synaptopathy after NIHL.
Bombyx mori Pupae Effectively Produce Recombinant AAV2/HBoV1 Vectors with a Bombyx mori Nuclear Polyhedrosis Virus Expression System
Recombinant adeno-associated virus (AAV) vectors have broad software prospects within the subject of gene remedy. The institution of low-cost and large-scale manufacturing is now the overall agenda for business. The baculovirus-insect cell/larva expression system has nice potential for these functions as a consequence of its scalability and predictable biosafety.
To ascertain a extra environment friendly manufacturing system, Bombyx mori pupae had been used as a brand new platform and contaminated with recombinant Bombyx mori nuclear polyhedrosis virus (BmNPV).
The manufacturing of a chimeric recombinant adeno-associated virus (rAAV) serotype 2/human bocavirus type-1 (HBoV1) vector was used to guage the effectivity of this new baculovirus expression vector (BEV)-insect expression system. For this function, we constructed two recombinant BmNPVs, which had been named rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP.
The yields of rAAV2/HBoV1 derived from the rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP co-infected BmN cells exceeded 2 × 104 vector genomes (VG) per cell. The rBmNPV/AAV2Rep-HBoV1Cap and rBmNPV/AAV2ITR-eGFP can specific stably for at the very least 5 passages. Considerably, rAAV2/HBoV1 may very well be effectively generated from BmNPV-infected silkworm larvae and pupae at common yields of two.52 × 1012 VG/larva and 4.6 × 1012 VG/pupa, respectively.
Nonetheless, the vectors produced from the larvae and pupae had a excessive share of empty particles, which means that additional optimization is required for this platform sooner or later. Our work exhibits that silkworm pupae, as an environment friendly bioreactor, have nice potential for software within the manufacturing of gene remedy vectors.
AAV2/9-mediated silencing of PMP22 prevents the event of pathological options in a rat mannequin of Charcot-Marie-Tooth illness 1 A
Charcot-Marie-Tooth illness 1 A (CMT1A) outcomes from a duplication of the PMP22 gene in Schwann cells and a deficit of myelination in peripheral nerves. Sufferers with CMT1A have decreased nerve conduction velocity, muscle losing, hand and foot deformations and foot drop strolling.
Right here, we consider the security and efficacy of recombinant adeno-associated viral vector serotype 9 (AAV2/9) expressing GFP and shRNAs focusing on Pmp22 mRNA in animal fashions of Charcot-Marie-Tooth illness 1 A.
Intra-nerve supply of AAV2/9 within the sciatic nerve allowed widespread transgene expression in resident myelinating Schwann cells in mice, rats and non-human primates. A bilateral therapy restore expression ranges of PMP22 akin to wild-type situations, leading to elevated myelination and prevention of motor and sensory impairments over a twelve-months interval in a rat mannequin of CMT1A.
AAV2-GFP Control Virus |
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| AAV-302 | Cell Biolabs | 50 ?L | EUR 1221.6 |
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Description: GFP control virus of AAV serotype 2. |
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AAV2-Cre Control Virus |
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| AAV-310 | Cell Biolabs | 50 ?L | EUR 1221.6 |
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Description: Cre control virus of AAV serotype 2. |
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AAV2-Luc Control Virus |
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| AAV-320 | Cell Biolabs | 50 ?L | EUR 1221.6 |
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Description: Luciferase control virus of AAV serotype 2. |
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AAV2-LacZ Control Virus |
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| AAV-342 | Cell Biolabs | 50 ?L | EUR 1221.6 |
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Description: LacZ control virus of AAV serotype 2. |
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Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E02A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E02A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E02A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Rat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Pig Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E07A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Porcine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Pig Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E07A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Porcine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Pig Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E07A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Porcine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Dog Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E08A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Canine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Dog Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E08A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Canine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Dog Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E08A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Canine Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E06A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E06A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E06A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Goat Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E03A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E03A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E03A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Mouse Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Human Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E01A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Human Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Human Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E01A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Human Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E09A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E09A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E09A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Monkey Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E04A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E04A0397-48 | BlueGene | 1 plate of 48 wells | EUR 624 |
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Description: A competitive ELISA for quantitative measurement of Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E04A0397-96 | BlueGene | 1 plate of 96 wells | EUR 822 |
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Description: A competitive ELISA for quantitative measurement of Rabbit Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Guinea pig Adeno Associated Virus type 2 Antibody (AAV2-Ab) ELISA kit |
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| E05A0397-192T | BlueGene | 192 tests | EUR 1524 |
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Description: A competitive ELISA for quantitative measurement of Guinea pig Adeno Associated Virus type 2 Antibody (AAV2-Ab) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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We noticed restricted off-target transduction and immune response utilizing the intra-nerve supply route. A mixture of beforehand characterised human pores and skin biomarkers is ready to discriminate between handled and untreated animals, indicating their potential use as a part of final result measures.