HIV silencing and cell survival signatures in infected T cell reservoirs.

Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling.

Ultrasound-Responsive Hydrogels for On-Demand Protein Release.

The development of tunable, ultrasound-responsive hydrogels that can deliver protein payload on-demand when exposed to focused ultrasound is described in this study. Reversible Diels-Alder linkers, which undergo a retro reaction when stimulated with ultrasound, were used to cross-link chitosan hydrogels with entrapped FITC-BSA as a model protein therapeutic payload. Two Diels-Alder linkage compositions with large differences in the reverse reaction energy barriers were compared to explore the influence of linker composition on ultrasound response.

Photocontrolled miR-148b nanoparticles cause apoptosis, inflammation and regression of Ras induced epidermal squamous cell carcinomas in mice.

Despite evidence that microRNAs (miRNAs) are essential in modulating tumorigenesis, a major challenge in cancer treatment is to achieve tumor-specific selectivity and efficient yet safe delivery of miRNAs in vivo. In this study, we have developed a light-inducible silver nanoparticle nucleic acid delivery system that demonstrates precise spatiotemporal control, high cellular uptake, low cytotoxicity, escape from endosomes and release of functional miRNA into the cytosol. Using this approach, we delivered exogenous miR-148b to induce apoptosis in Ras-expressing keratinocytes and murine squamous cell carcinoma cells while avoiding cytotoxicity in untransformed keratinocytes.

Alternating magnetic field mediated release of fluorophores from magnetic nanoparticles by hysteretic heating.

This study explores the use of differential heating of magnetic nanoparticles with different sizes and compositions (MFeO (M = Fe, Co)) for heteroplexed temporal controlled release of conjugated fluorophores from the surface of nanoparticles. By exploiting these differences, we were able to control the amount of hysteretic heating occurring with the distinct sets of magnetic nanoparticles using the same applied alternating magnetic field radio frequency (AMF-RF). Using thermally labile retro-Diels-Alder linkers conjugated to the surface of nanoparticles, the fluorescent payload from the different nanoparticles disengaged when sufficient energy was locally generated during hysteretic heating.

Combinatorial Delivery of miRNA-Nanoparticle Conjugates in Human Adipose Stem Cells for Amplified Osteogenesis.

It is becoming more apparent in tissue engineering applications that fine temporal control of multiple therapeutics is desirable to modulate progenitor cell fate and function. Herein, the independent temporal control of the co-delivery of miR-148b and miR-21 mimic plasmonic nanoparticle conjugates to induce osteogenic differentiation of human adipose stem cells (hASCs), in a de novo fashion, is described. By applying a thermally labile retro-Diels-Alder caging and linkage chemistry, these miRNAs can be triggered to de-cage serially with discrete control of activation times.

Collagen-infilled 3D printed scaffolds loaded with miR-148b-transfected bone marrow stem cells improve calvarial bone regeneration in rats.

Differentiation of progenitors in a controlled environment improves the repair of critical-sized calvarial bone defects; however, integrating micro RNA (miRNA) therapy with 3D printed scaffolds still remains a challenge for craniofacial reconstruction. In this study, we aimed to engineer three-dimensional (3D) printed hybrid scaffolds as a new ex situ miR-148b expressing delivery system for osteogenic induction of rat bone marrow stem cells (rBMSCs) in vitro, and also in vivo in critical-sized rat calvarial defects. miR-148b-transfected rBMSCs underwent early differentiation in collagen-infilled 3D printed hybrid scaffolds, expressing significant levels of osteogenic markers compared to non-transfected rBMSCs, as confirmed by gene expression and immunohistochemical staining.

Near-Infrared Photothermal Release of siRNA from the Surface of Colloidal Gold-Silver-Gold Core-Shell-Shell Nanoparticles Studied with Second-Harmonic Generation.

Photothermal release of oligonucleotides from the surface of plasmonic nanoparticles represents a promising platform for spatiotemporal controlled drug delivery. Here we demonstrate the use of novel gold-silver-gold core-shell-shell (CSS) nanoparticles to study the photothermal cleaving and release of micro-RNA (miRNA) mimics or small interfering RNA (siRNA) under nearinfrared (NIR) irradiation. The furan-maleimide-based Diels-Alder adduct cleaves thermally above 60 °C and is used to bind siRNA to the colloidal nanoparticle surface in water.

Comparison of thermally actuated retro-diels-alder release groups for nanoparticle based nucleic acid delivery.

The present study explores alternate pericyclic chemistries for tethering amine-terminal biomolecules onto silver nanoparticles. Employing the versatile tool of the retro-Diels-Alder (rDA) reaction, three thermally-labile cycloadducts are constructed that cleave at variable temperature ranges. While the reaction between furan and maleimide has widely been reported, the current study also evaluates the reverse reaction kinetics between thiophene-maleimide, and pyrrole-maleimide cycloadducts.

Monitoring the Photocleaving Dynamics of Colloidal MicroRNA-Functionalized Gold Nanoparticles Using Second Harmonic Generation.

Photoactivated drug delivery systems using gold nanoparticles provide the promise of spatiotemporal control of delivery that is crucial for applications ranging from regenerative medicine to cancer therapy. In this study, we use second harmonic generation (SHG) spectroscopy to monitor the light-activated controlled release of oligonucleotides from the surface of colloidal gold nanoparticles. MicroRNA is functionalized to spherical gold nanoparticles using a nitrobenzyl linker that undergoes photocleaving upon ultraviolet irradiation.

Primary immunodeficiency diseases in children: 15 year experience in a tertiary care medical center in Qatar.

Background: Primary immunodeficiency diseases (PID) are a group of heterogeneous, rare, genetic, mainly childhood disorders that affect specific components of immune system leading to serious complications.

Objectives: This study is aimed at describing the prevalence and the categories of PID, the ages of onset and the diagnosis, the clinical presentations, the treatment modalities and the overall outcome of affected patients.

Materials And Methods: A retrospective study was conducted on 131 pediatric patients (aged 0-14 years) diagnosed with PID at Hamad General Hospital during a 15-year period (1998-2012).