Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.

Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require a chimeric transcription factor (transactivator) that becomes activated by an inductor, which is not optimal for clinical translation due to their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control transgene expression in human stem cells.

Development of a digital platform to improve community response to overdose and prevention among harm reduction organizations.

The overdose crisis in the USA remains a growing and urgent public health concern. Over 108,000 people died due to overdose during 2021. Fatal and non-fatal overdoses are under-reported in the USA due to current surveillance methods.

The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition.

Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy.

sRNA/L1 retrotransposition: using siRNAs and miRNAs to expand the applications of the cell culture-based LINE-1 retrotransposition assay.

The cell culture-based retrotransposition reporter assay has been (and is) an essential tool for the study of vertebrate Long INterspersed Elements (LINEs). Developed more than 20 years ago, this assay has been instrumental in characterizing the role of LINE-encoded proteins in retrotransposition, understanding how ribonucleoprotein particles are formed, how host factors regulate LINE mobilization, etc. Moreover, variations of the conventional assay have been developed to investigate the biology of other currently active human retrotransposons, such as Alu and SVA.

Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons.

Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice.

The impact of transposable element activity on therapeutically relevant human stem cells.

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns.

Study of Transposable Elements and Their Genomic Impact.

Transposable elements (TEs) have been considered traditionally as junk DNA, i.e., DNA sequences that despite representing a high proportion of genomes had no evident cellular functions.

Buccal and coronal bone augmentation using forced eruption and buccal root torque: a case report.

The following case report describes the buccal and coronal bone augmentation around an irretrievable tooth using forced eruption and buccal root torque for immediate nonsubmerged implant placement. A mandibular left second premolar with degree 2 mobility, severe buccal bone resorption, and interproximal angular bony defects was subjected to forced eruption and buccal root torque. Five months after this process, the tooth was displaced 15 mm coronally and the root apex faced buccally.

Finite element analysis of the influence of implant inclination, loading position, and load direction on stress distribution.

The selection of the appropriate alignment of an implant and the position of implantation are vital for its longterm success. Excessive load is generated around inclined implants, causing microcracks in the bone, which result in implant loosening and eventual failure. This study was designed to analyze the stress distribution caused by varying the degree of inclination of an implant body and varying the loading position and direction, using the finite-element method of stress analysis.