Insertional mutagenesis using transfer DNA or transposable elements, which is an important tool in functional genomics and is well established in several crops, has not been developed in potato (Solanum tuberosum). Here, we report the application of the tobacco (Nicotiana tabacum) Tnt1 retrotransposon as an insertional mutagen in potato. The Tnt1 retrotransposon was introduced into a highly homozygous and self-compatible clone, 523-3, of the diploid wild potato species Solanum chacoense. Transposition of the Tnt1 elements introduced into 523-3 can be efficiently induced by tissue culture. Tnt1 preferentially inserted into genic regions in the potato genome and the insertions were stable during sexual reproduction, making Tnt1 an ideal mutagen in potato. Several distinct phenotypes associated with plant stature and leaf morphology were discovered in mutation screening from a total of 38 families derived from Tnt1-containing lines. We demonstrate that the insertional mutagenesis system based on Tnt1 and the 523-3 clone can be expanded to the genome-wide level to potentially tag every gene in the potato genome.
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http://dx.doi.org/10.1104/pp.113.221903 | DOI Listing |
Cancer Med
February 2025
Pulmonology and Thoracic Oncology Department, APHP Hôpital Tenon and Sorbonne Université, Paris, France.
Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.
Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).
Viruses
January 2025
Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus's infectivity and replication can be assessed by measuring postinfection luciferase signals.
View Article and Find Full Text PDFNat Med
January 2025
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.
View Article and Find Full Text PDFToxicol Appl Pharmacol
January 2025
Drug Safety Research & Development, Pfizer, Inc., Groton, CT 06340, USA.
One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Center for Advanced Innate Cell Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15).
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