Generation of two isogenic iPSC lines with either a heterozygous or a homozygous E280A mutation in the PSEN1 gene.

Alzheimer's disease (AD) is the most common form of dementia. Mutations in the gene PSEN1 encoding Presenilin1 are known to cause familial forms of AD with early age of onset. The most common mutation in the PSEN1 gene is the E280A mutation. iPSCs are an optimal choice for modeling AD, as they can be differentiated in vitro into neural cells. Here, we report the generation of two isogenic iPSC lines with either a homozygous or a heterozygous E280A mutation in the PSEN1 gene. The mutation was introduced into an iPSC line from a healthy individual using the CRISPR-Cas9 technology.Resource tableUnlabelled TableUnique stem cell lines identifier 1. BIONi010-C + homozygous E280A = BIONi010-C-29 2. BIONi010-C + heterozygous E280A = BIONi010-C-30Alternative names of stem cell lines 1. BIONi010-C E280 +/+ (homozygous line) 2. BIONi010-C E280 +/− (heterozygous line)InstitutionBioneer A/S Hørsholm Denmark and University of Copenhagen (UCPH) Copenhagen DenmarkContact information of distributorContact at Bioneer: Benjamin Schmid,[email protected]– Contact at UCPH: Kristine Freude,[email protected] of cell linesiPSCsOriginHumanCell SourceFibroblastsClonalityClonalMethod of reprogrammingEpisomal plasmids (Okita et al., 2011)Multiline rationaleMutated isogenic clonesGene modificationYESType of modificationInduced point mutationAssociated diseaseAlzheimer's disease (AD)Gene/locusPSEN1/Chr14:73664808Method of modificationCRISPR-Cas9Name of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock dateSeptember 2017Cell line repository/bank 1. BIONi010-C-29:https://hpscreg.eu/cell-line/BIONi010-C-29 2. BIONi010-C-30:https://hpscreg.eu/cell-line/BIONi010-C-30Ethical approvalThe study was approved by the Ethics Committee of the Capital Region of Denmark (H-4-2011-157), and written informed consent was obtained from the participant before enrolmen

Genetic Protection Modifications: Moving Beyond the Binary Distinction Between Therapy and Enhancement for Human Genome Editing

Current debate and policy surrounding the use of genetic editing in humans often relies on a binary distinction between therapy and human enhancement. In this paper, we argue that this dichotomy fails to take into account perhaps the most significant potential uses of CRISPR-Cas9 gene editing in humans. We argue that genetic treatment of sporadic Alzheimer’s disease, breast- and ovarian-cancer causing BRCA1/2 mutations and the introduction of HIV resistance in humans should be considered within a new category of genetic protection treatments. We find that if this category is not introduced, life-altering research might be unnecessarily limited by current or future policy. Otherwise ad hoc decisions might be made, which introduce a risk of unforeseen moral costs, and might overlook or fail to address some important opportunities

Novel traceable CRISPR-Cas9 engineered human embryonic stem cell line (E1C3 + hSEAP + 2xKO + pCD47), has potential to evade immune detection in pigs

Here we present the generation of a human embryonic stem cell line with the potential to escape immune rejection upon transplantation to an alternate species, in this case sus scrofa. For in vivo detection the cells were modified by CRISPR-Cas9 to express human secreted alkaline phosphatase. To avoid immune recognition and subsequent rejection by host, genes encoding hB2M and hCIITA were knocked out and the porcine gene for CD47 was introduced. Upon editing and subsequent culture, cells maintained molecular and phenotypic pluripotent charactaristics and a normal karyotype supporting viability and functionality of the engineered cell line