Genetics, Gene Therapy & Genetic Disease
- Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann–Pick disease type C1 mice
This work highlights the importance of CNS transduction for treatment of neurological diseases, a finding with significant clinical implications considering the long-lasting effects of gene therapy.
- Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids
Here, the authors evaluate prime editing in human adult stem cell–derived organoids. TP53 mutations are modeled in hepatocyte and colon organoids and the clinical application of prime editing is evaluated by repairing mutations in CFTR without genome-wide off-targets.
- Exosome-mediated delivery of CRISPR/Cas9 for targeting of oncogenic KrasG12D in pancreatic cancer
This work identifies the use of exosomes to specifically deliver CRISPR/Cas9 to target oncogenic KrasG12D mutation in pancreatic cancer as a nonviral therapeutic strategy.
- Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila
CRISPR knockout of msl-2 and epigenome analyses in Anopheles reveal that X chromosome dosage compensation in mosquitos and Drosophila is achieved by two different molecular mechanisms.
- PNKP is required for maintaining the integrity of progenitor cell populations in adult mice
Knockout of Pnkp in adult mice impairs the growth of hair follicle, spermatogonial, and neural progenitor populations.
- DNA damage in embryonic neural stem cell determines FTLDs’ fate via early-stage neuronal necrosis
DNA damage due to impairment of DNA damage repair functions in NSCs is carried over to neurons and triggers early-stage YAP-dependent neuronal necrosis (TRIAD) amplifying a chain of necrosis in FTLDs.
- Multifaceted regulation of hepatic lipid metabolism by YY1
This study shows that YY1 regulates hepatic lipid metabolism by directly or indirectly regulating the expression of several key upstream transcription factors and their coactivators.
- On the relation of gene essentiality to intron structure: a computational and deep learning approach
A deep learning classifier predicts gene essentiality by intron sequence. A unique set of intron features of essential genes was found and its importance demonstrated by a high-performing classifier.
- A novel canis lupus familiaris reference genome improves variant resolution for use in breed-specific GWAS
This paper describes the economical optimization of DNA extraction, short and long read sequencing, and bioinformatic assembly, which in turn improves mapping and variant resolution of short-read sequenced, same-breed dogs for association studies. This methodology is applicable for any investigators planning a genome-wide association study.
- Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models
This study used mice heterozygous for Tp53 mutations with different genetic backgrounds to investigate the genetic or stochastic factors that modify the penetrance of tumor formation by Tp53 mutation.