10 research outputs found
Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells
Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem-cell derived retina now offers the possibility to assess efficacy in human organoids in vitro. Here we test 6 AAV serotypes (AAV2/2, AAV2/9, AAV2/8, AAV2/8T(Y733F), AAV2/5 and ShH10) to determine their efficiency in transducing mouse and human pluripotent stem cell (PSC)-derived RPE and photoreceptor cells in vitro. All the serotypes tested were capable of transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and ShH10 achieved similarly robust transduction of human ESC-derived cone photoreceptors. Furthermore, we show that hESC-derived photoreceptors can be used to establish promoter specificity in human cells in vitro. The results of this study will aid capsid selection and vector design for pre-clinical evaluation of gene therapy approaches, such as gene editing, that require the use of human cells and tissues
Quantum simulation of the Hubbard model with dopant atoms in silicon
In quantum simulation, many-body phenomena are probed in controllable quantum
systems. Recently, simulation of Bose-Hubbard Hamiltonians using cold atoms
revealed previously hidden local correlations. However, fermionic many-body
Hubbard phenomena such as unconventional superconductivity and spin liquids are
more difficult to simulate using cold atoms. To date the required single-site
measurements and cooling remain problematic, while only ensemble measurements
have been achieved. Here we simulate a two-site Hubbard Hamiltonian at low
effective temperatures with single-site resolution using subsurface dopants in
silicon. We measure quasiparticle tunneling maps of spin-resolved states with
atomic resolution, finding interference processes from which the entanglement
entropy and Hubbard interactions are quantified. Entanglement, determined by
spin and orbital degrees of freedom, increases with increasing covalent bond
length. We find separation-tunable Hubbard interaction strengths that are
suitable for simulating strongly correlated phenomena in larger arrays of
dopants, establishing dopants as a platform for quantum simulation of the
Hubbard model.Comment: 6 pages, 5 figures. Supplementary: 13 pages, 7 figures. New version
with some additional discussion, accepted in Nature Communication
The rate of the F + H2 reaction at very low temperatures
International audienceThe prototypical F + H2 → HF + H reaction possesses a substantial energetic barrier (~800 K) and might therefore be expected to slow to a negligible rate at low temperatures. It is, however, the only source of interstellar HF, which has been detected in a wide range of cold (10-100 K) environments. In fact, the reaction does take place efficiently at low temperatures due to quantum-mechanical tunnelling. Rate constant measurements at such temperatures have essentially been limited to fast barrierless reactions, such as those between two radicals. Using uniform supersonic hydrogen flows we can now report direct experimental measurements of the rate of this reaction down to a temperature of 11 K, in remarkable agreement with state-of-the-art quantum reactive scattering calculations. The results will allow a stronger link to be made between observations of interstellar HF and the abundance of the most common interstellar molecule, H2, and hence a more accurate estimation of the total mass of astronomical objects