The next generation of CRISPR–Cas technologies and applications
A Pickar-Oliver, CA Gersbach - Nature reviews Molecular cell biology, 2019 - nature.com
The prokaryote-derived CRISPR–Cas genome editing systems have transformed our ability
to manipulate, detect, image and annotate specific DNA and RNA sequences in living cells …
to manipulate, detect, image and annotate specific DNA and RNA sequences in living cells …
Editing the genome without double-stranded DNA breaks
Genome editing methods have commonly relied on the initial introduction of double-
stranded DNA breaks (DSBs), resulting in stochastic insertions, deletions, and translocations …
stranded DNA breaks (DSBs), resulting in stochastic insertions, deletions, and translocations …
Programmable base editing of A• T to G• C in genomic DNA without DNA cleavage
The spontaneous deamination of cytosine is a major source of transitions from C• G to T• A
base pairs, which account for half of known pathogenic point mutations in humans. The …
base pairs, which account for half of known pathogenic point mutations in humans. The …
A large panel of isogenic APP and PSEN1 mutant human iPSC neurons reveals shared endosomal abnormalities mediated by APP β-CTFs, not Aβ
D Kwart, A Gregg, C Scheckel, EA Murphy, D Paquet… - Neuron, 2019 - cell.com
Familial Alzheimer's disease (fAD) results from mutations in the amyloid precursor protein
(APP) and presenilin (PSEN1 and PSEN2) genes. Here we leveraged recent advances in …
(APP) and presenilin (PSEN1 and PSEN2) genes. Here we leveraged recent advances in …
In vivo base editing of post-mitotic sensory cells
Programmable nucleases can introduce precise changes to genomic DNA through
homology-directed repair (HDR). Unfortunately, HDR is largely restricted to mitotic cells, and …
homology-directed repair (HDR). Unfortunately, HDR is largely restricted to mitotic cells, and …
Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency
A Reifschneider, S Robinson, B van Lengerich… - The EMBO …, 2022 - embopress.org
Haploinsufficiency of the progranulin (PGRN)‐encoding gene (GRN) causes frontotemporal
lobar degeneration (GRN‐FTLD) and results in microglial hyperactivation, TREM2 …
lobar degeneration (GRN‐FTLD) and results in microglial hyperactivation, TREM2 …
TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann–Pick type C1, and Batten disease
Lysosomes are cell organelles that degrade macromolecules to recycle their components. If
lysosomal degradative function is impaired, eg, due to mutations in lysosomal enzymes or …
lysosomal degradative function is impaired, eg, due to mutations in lysosomal enzymes or …
Homozygous might be hemizygous: CRISPR/Cas9 editing in iPSCs results in detrimental on-target defects that escape standard quality controls
The ability to precisely edit the genome of human induced pluripotent stem cell (iPSC) lines
using CRISPR/Cas9 has enabled the development of cellular models that can address …
using CRISPR/Cas9 has enabled the development of cellular models that can address …
Detection of deleterious on-target effects after HDR-mediated CRISPR editing
I Weisheit, JA Kroeger, R Malik, J Klimmt, D Crusius… - Cell reports, 2020 - cell.com
CRISPR genome editing is a promising tool for translational research but can cause
undesired editing outcomes, both on target at the edited locus and off target at other …
undesired editing outcomes, both on target at the edited locus and off target at other …
Development of hRad51–Cas9 nickase fusions that mediate HDR without double-stranded breaks
In mammalian cells, double-stranded DNA breaks (DSBs) are preferentially repaired
through end-joining processes that generally lead to mixtures of insertions and deletions …
through end-joining processes that generally lead to mixtures of insertions and deletions …