Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice

Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible

Hydrocarbon generation and migration from Barremian – Aptian source rocks, Northern Orange Basin, offshore Western South Africa: A 3d numerical modelling study

A 3D numerical modelling workflow was applied to the Barremian—Aptian source rock interval in a shelfal to lower slope area of the northern Orange Basin, offshore western South Africa. The main objective was to investigate the timing of hydrocarbon generation and migration. Hydrocarbon migration has previously been investigated in the south of the basin by relating gas escape features with structural elements as seen on seismic sections, but migration pathways are still poorly understood. The modelling study was based on data from three exploration wells (AO-1, AE-1 and AF-1) together with 42 2D seismic sections totalling 3537 km in length, and a 3D seismic cube covering an area of 750 sq. km. Modelled formation temperatures increase from north to south in the study area and were consistent with downhole temperatures at well locations. However, there is variation between measured and modelled values of vitrinite reflectance (VR), especially in the Turonian and Cenomanian intervals. The measured VR is lower than the modelled VR within the Turonian section in the north of the study area, suggesting that erosion has affected the thermal maturity of the sediments. However, in the Cenomanian interval, the measured VR is higher than the modelled VR. Uplift, increased erosion in the hinterland and sediment transport to the coastal areas resulted in Cenomanian progradation of the Orange Basin fill