ABSTRACT
Discovery of genomic safe harbor sites (SHSs) is fundamental for multiple transgene integrations, such as reporter genes, chimeric antigen receptors (CARs), and safety switches, which are required for safe cell products for regenerative cell therapies and immunotherapies. Here we identified and characterized potential SHS in human cells. Using the CRISPR-MAD7 system, we integrated transgenes at these sites in induced pluripotent stem cells (iPSCs), primary T and natural killer (NK) cells, and Jurkat cell line, and demonstrated efficient and stable expression at these loci. Subsequently, we validated the differentiation potential of engineered iPSC toward CD34+ hematopoietic stem and progenitor cells (HSPCs), lymphoid progenitor cells (LPCs), and NK cells and showed that transgene expression was perpetuated in these lineages. Finally, we demonstrated that engineered iPSC-derived NK cells retained expression of a non-virally integrated anti-CD19 CAR, suggesting that several of the investigated SHSs can be used to engineer cells for adoptive immunotherapies.
ABSTRACT
Flexible pressure sensors have attracted tremendous attention from researchers for their widely applications in tactile artificial intelligence, electric skin, disease diagnosis, and healthcare monitoring. Obtaining flexible pressure sensors with high sensitivity in a low cost and convenient way remains a huge challenge. In this paper, the composite dielectric layer based on the mixture of carbon nanotubes (CNTs) with different aspect ratios and polydimethylsiloxane (PDMS) was employed in flexible capacitive pressure sensor to increase its sensitivity. In addition, the screen printing instead of traditional etching based methods was used to prepare the electrodes array of the sensor. The results showed that the aspect ratio and weight fraction of the CNTs play an important role in improving the sensitivity of the printed capacitive pressure sensor. The prepared capacitive sensor with the CNTs/PDMS composite dielectric layer demonstrated a maximum sensitivity of 2.9 kPa-1 in the pressure range of 0-450 Pa, by using the CNTs with an aspect ratio of 1250-3750 and the weight fraction of 3.75%. The mechanism study revealed that the increase of the sensitivity of the pressure sensor should be attributed to the relative permittivity increase of the composite dielectric layer under pressure. Meanwhile, the printed 3 × 3 and 10 × 10 sensor arrays showed excellent spatial resolution and uniformity when they were applied to measure the pressure distribution. For further applications, the flexible pressure sensor was integrated on an adhesive bandage to detect the finger bending, as well as used to create Morse code by knocking the sensor to change their capacitance curves. The printed and flexible pressure sensor in this study might be a good candidate for the development of tactile artificial intelligence, intelligent medical diagnosis systems and wearable electronics.
