A5077269946- CAR-T cell therapy research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Neurobiology and Insect Physiology Research
- Receptor Mechanisms and Signaling
- Complement system in diseases
- Ion Channels and Receptors
- Pluripotent Stem Cells Research
- Platelet Disorders and Treatments
- Virus-based gene therapy research
- Insect Resistance and Genetics
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Pharmacological Effects and Assays
- Ion channel regulation and function
- Xenotransplantation and immune response
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Pain Mechanisms and Treatments
- Immunotherapy and Immune Responses
- Renal and related cancers
Poseida Therapeutics (United States)
2016-2023
Universidade Estadual de Campinas (UNICAMP)
2023
Transposagen Biopharmaceuticals (United States)
2009-2018
University of Pennsylvania
1998-2016
University of Kentucky
2011-2014
The University of Texas Medical Branch at Galveston
2012
Shanghai Tenth People's Hospital
2011
University of Minnesota
2011
Tongji University
2011
Medical College of Wisconsin
2011
AbstractLong interspersed nuclear elements (LINEs or L1s) comprise approximately 17% of human DNA; however, only about 60 the ∼400,000 L1s are mobile. Using a retrotransposition assay in cultured cells, we demonstrate that L1-encoded proteins predominantly mobilize RNA encodes them. At much lower levels, can act trans to promote mutant and other cellular mRNAs, creating processed pseudogenes. Mutant L1 RNAs mobilized at 0.2 0.9% frequency wild-type L1s, whereas frequencies (ca. 0.01 0.05%...
Long Interspersed Element 1 (L1) is a retrotransposon that comprises approximately 17% of the human genome. Despite its abundance in mammalian genomes, relatively little understood about L1 retrotransposition vivo. To study timing and tissue specificity retrotransposition, we created transgenic mouse rat models containing or elements controlled by their endogenous promoters. Here, demonstrate abundant RNA both germ cells embryos. However, integration events usually occur embryogenesis rather...
L1 retrotransposons are autonomous retroelements that active in the human and mouse genomes. Previously, we developed a cultured cell assay uses neomycin phosphotransferase (neo) retrotransposition cassette to determine relative retrotransposition frequencies among various elements. Here, describe new an enhanced green fluorescent protein (EGFP) kinetics cells. We show is not detected cells during first 48 h post-transfection, but then proceeds at continuous high rate for least 16 days....
L1 retrotransposons are pervasive in the human genome. Approximately 25% of recent insertions genome inverted and truncated at 5′ end element, but mechanism inversion has been a complete mystery. We analyzed inversions from genomic database discovered several findings that suggested for creation inversions, which we call twin priming. Twin priming is consequence target primed reverse transcription (TPRT), coupled transcription/integration reaction elements thought to use during their...
Unlike human L1 retrotransposons, the 5′ UTR of mouse elements contains tandem repeats ∼200 bp in length called monomers. Multiple subfamilies exist which are distinguished by their monomer sequences. We previously described a young subfamily, T F ∼1800 active among its 3000 full-length members. Here we characterize novel subfamily elements, G , has unique sequence and unusual patterns organization. A majority these also have polymorphism ORF1. Polymorphism analysis various subspecies...
The use of T cells from healthy donors for allogeneic chimeric antigen receptor (CAR-T) cell cancer therapy is attractive because donor can produce versatile off-the-shelf CAR-T treatments. To maximize safety and durability products, the endogenous major histocompatibility complex class I molecules are often removed via knockout beta constant (TRBC) (or alpha [TRAC]) B2M, respectively. However, gene editing tools (e.g., CRISPR-Cas9) display poor fidelity, which may result in dangerous...
98 Background: P-PSMA-101 is an autologous CAR-T therapy targeting PSMA, with a high percentage of stem cell memory T cells (T SCM ) associated efficacy, safety, and bone homing (particularly relevant to prostate cancer). It manufactured using novel non-viral transposon system (piggyBac) that creates products. Genes are inserted encoding PSMA-targeted Centyrin CAR, iCasp9-based safety switch, DHFR purify cells. completely eliminated tumors in intractable murine models cancer, providing...
To study integration of the human LINE-1 retrotransposon (L1) in vivo, we developed a transgenic mouse model L1 retrotransposition that displays de novo somatic insertions at high frequency, occasionally several per mouse. We mapped 3′ sites 51 by Thermal Asymmetric Interlaced PCR (TAIL–PCR). Analysis locations revealed broad genomic distribution with modest preference for intergenic regions. characterized complete structures 33 events. Our results highlight large number highly truncated...
Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular anions, it highly expressed in lung tissue. However, not clear whether endogenous SOD3 can influence PAH. Here we examined effect knockout on hypoxia-induced PAH mice a loss-of-function gene mutation (SOD3 E124D ) monocrotaline (40 mg/kg)-induced rats. significantly...
Significance Acquired thrombotic thrombocytopenic purpura (TTP) is primarily caused by autoantibodies that inhibit the ability of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) to proteolyze von Willebrand factor (VWF). The molecular mechanism inhibition not known. We used hydrogen–deuterium exchange mass spectrometry (HX MS) method determine at near–single-residue resolution epitope three monoclonal anti-ADAMTS13 isolated from TTP patients....
Most new genes arise by duplication of existing gene structures, after which relaxed selection on the copy frequently leads to mutational inactivation duplicate; only rarely will a with modified function emerge. Here we describe unique mechanism creation, whereby combinations functional domains are assembled at RNA level from distinct genes, and resulting chimera is then reverse transcribed integrated into genome L1 retrotransposon. We characterized novel gene, termed PIP5K1A PSMD4-like (...
BACKGROUND Acquired thrombotic thrombocytopenia purpura (TTP) is a life‐threatening illness caused by autoantibodies that decrease the activity of ADAMTS13, von Willebrand factor–cleaving protease. Despite efficacy plasma exchange, mortality remains high and relapse common. Improved therapies may come from understanding diversity pathogenic on molecular or genetic level. Cloning comprehensive repertoires patient can provide necessary tools for studying immunobiology disease developing animal...
In wild type (WT) tracheal epithelial cells, ciliary basal bodies are oriented such that all cilia on the cell surface beat in same upward direction. This precise alignment of and, as a result, axoneme, is termed rotational planar polarity (PCP). Rotational PCP multi‐ciliated cells trachea perturbed rats lacking myosin Id (Myo1d). Myo1d localized F‐actin and body rich subapical cortex ciliated cell. Scanning transmission electron microscopy knock out (KO) revealed unidirectional bending...