Search Our Scientific Publications & Authors

Sci Rep 2021 Apr 9;11(1):7825. Epub 2021 Apr 9.

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Khorasan Razavi, Iran.

The therapeutic potential of mesenchymal stem cells (MSCs) is out of the question. Yet, recent drawbacks have resulted in a strategic shift towards the application of MSC-derived cell-free products such as extracellular vesicles (EVs). Recent reports revealed that functional properties of MSCs, including EV secretion patterns, correlate with microenvironmental cues. Read More

Ultrasound Med Biol 2021 Mar 31. Epub 2021 Mar 31.

Department of Medicine, John A. Burns School of Medicine, Honolulu, Hawaii, USA. Electronic address:

We compared focused and unfocused ultrasound-targeted microbubble destruction (UTMD) for delivery of reporter plasmids to the liver and heart in mice. Optimal hepatic expression was seen with double-depth targeting at 5 and 13 mm in vivo, incorporating a low pulse repetition frequency and short pulse duration. Reporter expression was similar, but the transfection patterns were distinct, with intense foci of transfection using focused UTMD (F-UTMD). Read More

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Genomics and Postgenomic Technologies, Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE). Read More

J Biomed Res 2020 Dec;35(2):163-173

Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583-0908, USA.

Since genetic engineering of pigs can benefit both biomedicine and agriculture, selecting a suitable gene promoter is critically important. The cytomegalovirus (CMV) promoter, which can robustly drive ubiquitous transgene expression, is commonly used at present, yet recent reports suggest tissue-specific activity in the pig. The objective of this study was to quantify ZsGreen1 protein (in lieu of CMV promoter activity) in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site. Read More

Brain Pathol 2021 Mar 16:e12946. Epub 2021 Mar 16.

Department of Neuroscience, Erasmus MC, Rotterdam, Netherlands.

Purkinje cells are the primary processing units of the cerebellar cortex and display molecular heterogeneity that aligns with differences in physiological properties, projection patterns, and susceptibility to disease. In particular, multiple mouse models that feature Purkinje cell degeneration are characterized by incomplete and patterned Purkinje cell degeneration, suggestive of relative sparing of Purkinje cell subpopulations, such as those expressing Aldolase C/zebrinII (AldoC) or residing in the vestibulo-cerebellum. Here, we investigated a well-characterized Purkinje cell-specific mouse model for spinocerebellar ataxia type 1 (SCA1) that expresses human ATXN1 with a polyQ expansion (82Q). Read More

J Neurogenet 2021 Mar 10:1-14. Epub 2021 Mar 10.

Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.

Larval are used as a genetically accessible study case in many areas of biological research. Here we report a fast, robust and user-friendly procedure for the whole-body multi-fluorescence imaging of larvae; the protocol has been optimized specifically for larvae by systematically tackling the pitfalls associated with clearing this small but cuticularized organism. Tests on various fluorescent proteins reveal that the recently introduced monomeric infrared fluorescent protein (mIFP) is particularly suitable for our approach. Read More

Pest Manag Sci 2021 Mar 4. Epub 2021 Mar 4.

Arthropod Genetics Group, The Pirbright Institute, Woking, UK.

Background: Previous genetic pest management (GPM) systems in diamondback moth (DBM) have relied on expressing lethal proteins ('effectors') that are 'cell-autonomous', that is, they do not leave the cell in which they are expressed. To increase the flexibility of future GPM systems in DBM, we aimed to assess the use of a non-cell-autonomous, invertebrate-specific, neurotoxic effector - the scorpion toxin AaHIT. This AaHIT effector was designed to be secreted by expressing cells, potentially leading to effects on distant cells, specifically neuromuscular junctions. Read More

J Integr Plant Biol 2021 Mar 2. Epub 2021 Mar 2.

Institute of Crop Science, Chinese Academy of Agricultural Sciences, National Key Facility for Crop Gene Resources and Genetic Improvement, Beijing, 100081, China.

Genome editing by CRISPR/Cas has revolutionized functional gene analysis and genetic improvement. While reporter-assisted CRISPR/Cas systems can greatly facilitate the selection of genome-edited plants produced via stable transformation, this approach has not been well established in seed crops. Here, we established the Seed Fluorescence Reporter (SFR)-assisted CRISPR/Cas9 systems in maize (Zea mays L. Read More

Genome Biol 2021 Feb 4;22(1):56. Epub 2021 Feb 4.

School of Life Sciences, University of Warwick, Coventry, UK.

Background: Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. Read More

Elife 2021 Feb 1;10. Epub 2021 Feb 1.

Department of Developmental Biology and Department of Genetics, Washington University in St. Louis, St. Louis, United States.

Across species, lifespan is highly variable among individuals within a population. Even genetically identical reared in homogeneous environments are as variable in lifespan as outbred human populations. We hypothesized that persistent inter-individual differences in expression of key regulatory genes drives this lifespan variability. Read More

Biotechnol Bioeng 2021 Apr 2;118(4):1693-1706. Epub 2021 Feb 2.

Department of Chemical and Biological Engineering, Villanova University, Villanova, Pennsylvania, USA.

Retroviral gene delivery is widely used in T cell therapies for hematological cancers. However, viral vectors are expensive to manufacture, integrate genes in semirandom patterns, and their transduction efficiency varies between patients. In this study, several nonviral gene delivery vehicles, promoters, and additional variables were compared to optimize nonviral transgene delivery and expression in both Jurkat and primary T cells. Read More

Plasmid 2021 Mar 17;114:102556. Epub 2021 Jan 17.

Villanova University, Department of Chemical & Biological Engineering, United States. Electronic address:

The innate immune response is an essential defense mechanism that allows cells to detect pathogen-associated molecular patterns (PAMPs) like endotoxin or cytosolic DNA and then induce the expression of defensive genes that restrict the replication of viruses and other pathogens. However, the therapeutic DNA used in some gene therapy treatments can also trigger the innate immune response, which activates host cell genes that may inhibit transgene expression. The goal of this study was to enhance transgene expression by inhibiting key components of the innate immune response with small molecule inhibitors (iCRT14, curcumin, Amlexanox, H-151, SC-514, & VX-702). Read More

PLoS One 2021 14;16(1):e0245446. Epub 2021 Jan 14.

Department of Plant Science, Research Institute for Agriculture and Life Sciences, and Plant Genomics and Breeding Institute, Seoul National University, Seoul, Republic of Korea.

The resveratrol-producing rice (Oryza sativa L.) inbred lines, Iksan 515 (I.515) and Iksan 526 (I. Read More

Cell 2021 Jan 29;184(1):272-288.e11. Epub 2020 Dec 29.

Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA.

Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic atlas of landmarks). Read More

Plant Commun 2020 May 18;1(3):100046. Epub 2020 Apr 18.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

ETHYLENE INSENSITIVE2 (EIN2) is a key component of ethylene signaling whose activity is inhibited upon phosphorylation of Ser and Ser by the Raf-like CONSTITUTIVE TRIPLE-RESPONSE 1 (CTR1) in the absence of ethylene. Ethylene prevents CTR1 activity and thus EIN2 phosphorylation, and subcellular trafficking of a proteolytically cleaved EIN2 C terminus (EIN2-C) from the endoplasmic reticulum to the nucleus and processing bodies triggers ethylene signaling. Here, we report an unexpected complexity of EIN2-activated ethylene signaling. Read More

Gynecol Oncol 2021 Feb 17;160(2):520-529. Epub 2020 Dec 17.

Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 3E6, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. Electronic address:

Objective: Chimeric antigen receptor (CAR)-T cell strategies ideally target a surface antigen that is exclusively and uniformly expressed by tumors; however, no such antigen is known for high-grade serous ovarian carcinoma (HGSC). A potential solution involves combinatorial antigen targeting with AND or OR logic-gating. Therefore, we investigated co-expression of CA125, Mesothelin (MSLN) and Folate Receptor alpha (FOLRA) on individual tumor cells in HGSC. Read More

Front Immunol 2020 30;11:579872. Epub 2020 Nov 30.

Preclinical R&D, GSK, Rixensart, Belgium.

Replication-deficient chimpanzee adenovirus (ChAd) vectors represent an attractive vaccine platform and are thus employed as vaccine candidates against several infectious diseases. Since inducing effective immunity depends on the interplay between innate and adaptive immunity, a deeper understanding of innate immune responses elicited by intramuscularly injected ChAd vectors in tissues can advance the platform's development. Using different candidate vaccines based on the Group C ChAd type 155 (ChAd155) vector, we characterized early immune responses in injected muscles and draining lymph nodes (dLNs) from mice, and complemented these analyses by evaluating cytokine responses and gene expression patterns in peripheral blood from ChAd155-injected macaques. Read More

Dev Biol 2021 Mar 13;471:119-137. Epub 2020 Dec 13.

Division of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address:

Diversity of neural crest derivatives has been studied with a variety of approaches during embryonic development. In mammals Cre-LoxP lineage tracing is a robust means to fate map neural crest relying on cre driven from regulatory elements of early neural crest genes. Sox10 is an essential transcription factor for normal neural crest development. Read More

Methods Mol Biol 2021 ;2245:23-38

Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Cartilage is a specialized skeletal tissue with a unique extracellular matrix elaborated by its resident cells, chondrocytes. The tissue presents in several forms, including growth plate and articular cartilage, wherein chondrocytes follow a differential differentiation program and have different fates. The induction of gene modifications in cartilage specifically relies on mouse transgenes and knockin alleles taking advantages of transcriptional elements primarily active in chondrocytes at a specific differentiation stage or in a specific cartilage type. Read More

Comput Struct Biotechnol J 2020 12;18:3632-3648. Epub 2020 Nov 12.

University of Natural Resources and Life Sciences, Vienna, Austria.

Chinese Hamster Ovary (CHO) cell lines are considered to be the preferred platform for the production of biotherapeutics, but issues related to expression instability remain unresolved. In this study, we investigated potential causes for an unstable phenotype by comparing cell lines that express stably to such that undergo loss in titer across 10 passages. Factors related to transgene integrity and copy number as well as the genomic profile around the integration sites were analyzed. Read More

Front Microbiol 2020 13;11:591619. Epub 2020 Nov 13.

Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, China.

Rice stripe virus (RSV) causes rice stripe disease, which is one of the most serious rice diseases in eastern Asian countries. It has been shown that overexpression of RSV coat protein (CP) in rice plants enhances resistance against virus infection. However, the detailed mechanism underlying RSV CP-mediated virus resistance remains to be determined. Read More

Stem Cells Transl Med 2020 Nov 16. Epub 2020 Nov 16.

Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, USA.

Naturally occurring disease in pet dogs is an untapped and unique resource for stem cell-based regenerative medicine translational research, given the many similarities and complexity such disease shares with their human counterparts. Canine-specific regulators of somatic cell reprogramming and pluripotency maintenance are poorly understood. While retroviral delivery of the four Yamanaka factors successfully reprogrammed canine embryonic fibroblasts, adult stromal cells remained resistant to reprogramming in spite of effective viral transduction and transgene expression. Read More

Front Plant Sci 2020 14;11:570778. Epub 2020 Oct 14.

Trait Product Development, Dow Agrosciences, Indianapolis, IN, United States.

The selection of transcription terminators (TTs) for pairing with high expressing constitutive promoters in chimeric constructs is crucial to deliver optimal transgene expression in plants. In this study, the use of the native combinations of four polyubiquitin gene promoters and corresponding TTs resulted in up to >3-fold increase in transgene expression in maize. Of the eight polyubiquitin promoter and TT regulatory elements utilized, seven were novel and identified from the polyubiquitin genes of , , and . Read More

Plants (Basel) 2020 Nov 3;9(11). Epub 2020 Nov 3.

Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

is commonly used as an herbal tea component or traditional medicine for treating several diseases, including diabetes. Polyacetylenes have two or more carbon-carbon triple bonds or alkynyl functional groups and are mainly derived from fatty acid and polyketide precursors. Here, we report the cloning of full-length cDNAs that encode Δ12-fatty acid acetylenase (designated BPFAA) and Δ12-oleate desaturase (designated BPOD) from , which we predicted to play a role in the polyacetylene biosynthetic pathway. Read More

Eur J Neurosci 2020 12 11;52(12):4824-4839. Epub 2020 Nov 11.

Division of Neuropharmacology and Neurological Disorders, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

Retrogradely-transducing viral vectors are versatile tools for anatomical and functional interrogations of neural circuits. These vectors can be applied in nonhuman primates (NHPs), powerful model species for neuroscientific studies with limited genetic tractability, but limited data are available regarding the tropism and transgene expression patterns of such viruses after injections in NHP brains. Consequently, NHP researchers must often rely on related data available from other species for experimental planning. Read More

Nat Rev Neurosci 2020 12 27;21(12):669-681. Epub 2020 Oct 27.

Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Recombinant viruses are the workhorse of modern neuroscience. Whether one would like to understand a neuron's morphology, natural activity patterns, molecular composition, connectivity or behavioural and physiologic function, most studies begin with the injection of an engineered virus, often an adeno-associated virus or herpes simplex virus, among many other types. Recombinant viruses currently enable some combination of cell type-specific, circuit-selective, activity-dependent and spatiotemporally resolved transgene expression. Read More

BMC Genet 2020 10 22;21(Suppl 1):96. Epub 2020 Oct 22.

Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, 630090, Russia.

Background: The Drosophila central nervous system (CNS) is a convenient model system for the study of the molecular mechanisms of conserved neurobiological processes. The manipulation of gene activity in specific cell types and subtypes of the Drosophila CNS is frequently achieved by employing the binary Gal4/UAS system. However, many Gal4 driver lines available from the Bloomington Drosophila Stock Center (BDSC) and commonly used in Drosophila neurobiology are still not well characterized. Read More

Plant Mol Biol 2020 Dec 30;104(6):575-582. Epub 2020 Sep 30.

Laboratory of Plant Molecular Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.

Key Message: In the ros1-defective mutant, DREB1A repression by the transgene-induced promoter methylation of ice1-1 became inheritable across generations even in the absence of the causative transgene NICE1. Transgene silencing (TGS) is a widely observed event during plant bioengineering, which is presented as a gradual decrease in ectopic gene expression across generations and occasionally coupled with endogenous gene silencing based on DNA sequence similarity. TGS is known to be established by guided DNA methylation machinery. Read More

Sci Adv 2020 Sep 30;6(40). Epub 2020 Sep 30.

Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

Spatial patterns of gene expression in living organisms orchestrate cell decisions in development, homeostasis, and disease. However, most methods for reconstructing gene patterning in 3D cell culture and artificial tissues are restricted by patterning depth and scale. We introduce a depth- and scale-flexible method to direct volumetric gene expression patterning in 3D artificial tissues, which we call "heat exchangers for actuation of transcription" (HEAT). Read More

Mol Cell 2020 10 18;80(2):246-262.e4. Epub 2020 Sep 18.

Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA; Tata Institute for Genetics and Society, University of California, San Diego, La Jolla, CA, USA. Electronic address:

CRISPR-Cas9-based gene drive systems possess the inherent capacity to spread progressively throughout target populations. Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs). Read More