8 research outputs found
Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice
Fabry disease is a lysosomal storage disorder caused by a deficiency of a-galactosidase A (a-gal A) activity that results in progressive globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background a-gal A activity. Next, we transplanted normal human CD34(+) cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-a-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma a-gal A activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb(3) reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.Fil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yoshimitsu, Makoto. Kagoshima University; Japón. University Health Network; CanadáFil: Mizue, Nobuo. University Health Network; CanadáFil: Au, Bryan C. Y.. University Health Network; CanadáFil: Wang, James C. M.. University Health Network; CanadáFil: Fan, Xin. University Health Network; CanadáFil: Takenaka, Toshihiro. Kagoshima University; JapónFil: Medin, Jeffrey A. University Health Network; Canadá. University of Toronto; Canad
Spin-Polarized Radicals with Extremely Long Spin-Lattice Relaxation Time at Room Temperature in a Metal-Organic Framework
The generation of spin polarization is key in quantum information science and dynamical nuclear polarization. Polarized electron spins with long spin-lattice relaxation times (T1) at room temperature are important for these applications, but have been difficult to achieve. We report the realization of spin-polarized radicals with extremely long T1 at room temperature in a metal-organic framework (MOF) in which azaacene chromophores are densely integrated. Persistent radicals are generated in the MOF by charge separation after photoexcitation. Spin polarization of triplet generated by photoexcitation are successfully transferred to the persistent radicals. Pulse ESR measurements reveal that the T1 of the polarized radical in the MOF is as long as 274 s at room temperature. The achievement of extremely long spin polarization in MOFs with nanopores accessible to guest molecules will be an important cornerstone for future highly sensitive quantum sensing and efficient dynamic nuclear polarization
Spin-Polarized Radicals with Extremely Long Spin–Lattice Relaxation Time at Room Temperature in a Metal–Organic Framework
The generation of spin polarization
is key in quantum information
science and dynamic nuclear polarization. Polarized electron spins
with long spin–lattice relaxation times (T1) at room temperature are important for these applications
but have been difficult to achieve. We report the realization of spin-polarized
radicals with extremely long T1 at room
temperature in a metal–organic framework (MOF) in which azaacene
chromophores are densely integrated. Persistent radicals are generated
in the MOF by charge separation after photoexcitation. Spin polarization
of a triplet generated by photoexcitation is successfully transferred
to the persistent radicals. Pulse electron spin resonance measurements
reveal that the T1 of the polarized radical
in the MOF is as long as 214 μs with a relatively long spin–spin
relaxation time T2 of the radicals of
up to 0.98 μs at room temperature. The achievement of extremely
long spin polarization in MOFs with nanopores accessible to guest
molecules will be an important cornerstone for future highly sensitive
quantum sensing and efficient dynamic nuclear polarization