Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.

Chimeric antigen receptor (CAR) T cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate the CAR into the T cell receptor alpha constant (TRAC) locus to take advantage of the endogenous promoter and regulatory elements for CAR expression. This method used adeno-associated viral (AAV) vectors based on AAV6 to deliver the donor template encoding the CAR construct.

Alzheimer's disease induced neurons bearing mutations exhibit reduced excitability.

Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD progression, the link between mutations and neuronal excitability remains to be fully elucidated.

High-Throughput , and Screen of Adeno-Associated Virus Vectors Based on Physical and Functional Transduction.

Adeno-associated virus (AAV) vectors are quickly becoming the vectors of choice for therapeutic gene delivery. To date, hundreds of natural isolates and bioengineered variants have been reported. While factors such as high production titer and low immunoreactivity are important to consider, the ability to deliver the genetic payload (physical transduction) and to drive high transgene expression (functional transduction) remains the most important feature when selecting AAV variants for clinical applications.

Drosophila subobscura flies adapted to low lead concentration carry no fitness cost.

As a response to the long-term presence of heavy metals in the environment, populations can evolve resistance. Its maintenance may have detrimental effect on population's fitness, causing a fitness cost. Lead is one of the widely distributed elements in the environment exhibiting high toxicity on organisms.

Imidacloprid does not induce Cyp genes involved in insecticide resistance of a mutant Drosophila melanogaster line.

Certain xenobiotics have the capacity to induce the expression of genes involved in various biological phenomena, including insecticide resistance. The induction potential of different chemicals, among them different insecticides, has been documented for a number of insect species. In this study, we have analyzed the induction potential of Imidacloprid, a widely used member of the neonicotinoid insecticide family.

Use of mutagenesis, genetic mapping and next generation transcriptomics to investigate insecticide resistance mechanisms.

Insecticide resistance is a worldwide problem with major impact on agriculture and human health. Understanding the underlying molecular mechanisms is crucial for the management of the phenomenon; however, this information often comes late with respect to the implementation of efficient counter-measures, particularly in the case of metabolism-based resistance mechanisms. We employed a genome-wide insertional mutagenesis screen to Drosophila melanogaster, using a Minos-based construct, and retrieved a line (MiT[w(-)]3R2) resistant to the neonicotinoid insecticide Imidacloprid.

Monitoring of the genetic structure of natural populations: change of the effective population size and inversion polymorphism in Drosophila subobscura.

We analyzed changes in the genetic structure and effective population size of two ecologically distinct populations of Drosophila subobscura over several years. Population sizes of D. subobscura in beech and oak wood habitats for a period of 6 years were estimated by the capture-mark-release-recapture method.