Publications by authors named "Dakota Newman"
We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.
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- In patients transitioning from acute to chronic hepatitis B virus (HBV) infection, CD8+ T cells fail to effectively eliminate the virus, necessitating new, functional T cell responses for a potential cure.
- Researchers developed a therapeutic HBV vaccine, AdC6-gDHBV2, using a chimpanzee adenovirus vector that incorporates HSV glycoprotein D to enhance CD8+ T cell responses.
- In preclinical tests, this vaccine induced significant reductions in circulating HBV DNA and surface antigens, demonstrating its effectiveness even when administered long after the initial infection.
Article Synopsis
- Researchers addressed the limited access to lower motor neurons (LMNs) in the mammalian spinal cord by creating single cell multiome datasets from mouse and macaque spinal cords to identify enhancers for different neuronal populations.* -
- They cloned identified enhancers into viral vectors and conducted functional tests in mice to screen for effective candidates, which were then validated in rats and macaques.* -
- This new toolkit for labeling LMNs and upper motor neurons (UMNs) can facilitate future research on cell function across species and contribute to potential therapies for neurodegenerative diseases in humans.*
Article Synopsis
- The mammalian cortex consists of different cell types that have specific properties, which are important for understanding how the cortex functions in both health and disease.
- Researchers utilized data from mouse and human studies to identify marker genes and enhancers for various cortical cell types, creating a comprehensive set of tools for targeting these cells specifically.
- They introduced fifteen new transgenic driver lines, two new reporter lines, and over 800 enhancer AAVs, facilitating a wide range of experimental approaches to study the mammalian cortex and its functions.
Article Synopsis
- Recent studies on human cortex have shown that GABAergic neurons have a complex hierarchical organization with various subclasses and specific types.
- Researchers used advanced techniques to study these neurons in human brain slices, combining viral labeling and single-cell RNA sequencing.
- The findings revealed detailed differences within GABAergic neuron types, including variations between human and mouse neurons and highlighted the need for comprehensive analysis to better understand brain cell properties.
Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants.
View Article and Find Full Text PDFAdeno-associated virus (AAV) vector-mediated gene transfer is lessening the impact of monogenetic disorders. Human AAV gene therapy recipients commonly mount immune responses to AAV or the encoded therapeutic protein, which requires transient immunosuppression. Most efforts to date have focused on blunting AAV capsid-specific T cell responses, which have been implicated in elimination of AAV-transduced cells.
View Article and Find Full Text PDFBackground: Chronic hepatitis B virus (HBV) infection (CHB) is a significant public health problem that could benefit from treatment with immunomodulators. Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins.
Methods: Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens.