Genetic Engineering Publications - GEG Tech top picks

Although gene editing technologies hold promise for preventing and treating debilitating inherited diseases, a new study reveals limitations that must be overcome before gene editing to establish a pregnancy can be considered safe or effective. The study, published recently in the journal Nature Communications, involved sequencing the genomes of early human embryos that had undergone genome editing using the CRISPR gene editing tool. The work calls into question the accuracy of a DNA reading procedure that relies on amplifying a small amount of DNA for genetic testing. This scientific method commonly used to analyze a tiny amount of DNA in early human embryos fails to accurately reflect genetic changes. In addition, the study also reveals that gene editing to correct disease-causing mutations in early human embryos can also result in unintended and potentially harmful changes to the genome. The findings raise a new scientific basis for caution for any scientist who might be about to use genetically modified embryos to establish pregnancies.

In mammals, parthenogenesis is limited because of problems arising from genomic imprinting. Here, the scientists report live mammalian offspring derived from single unfertilized eggs. This was achieved by the targeted DNA methylation rewriting of seven imprinting control regions. By designing guide RNAs with protospacer adjacent motif (PAM) sequences matching one allele but not the other, dCas9-Dnmt3a or dCpf1-Tet1 enables targeted DNA methylation editing in an allele-specific manner. The success of parthenogenesis in mammals opens many opportunities in agriculture, research, and medicine.

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.

Preimplantation genetic testing has become standard care for parents at risk of having children with chromosomal and single gene disorders. Embryos created via in vitro fertilization (IVF) can be genetically screened for abnormalities prior to implantation, thus minimizing the risk of inherited genetic disease. However, most human traits are highly polygenic. Preimplantation genetic testing for polygenic risk (PGT-P) is an emerging technology that can screen the entire genome of an embryo and uses polygenic indices to predict the likelihood of a particular polygenic phenotype occurring if used in IVF. Targeted outcomes range from risk of cancer and other diseases to a child's potential educational attainment. Although PGT-P is available in IVF clinics around the world, it remains unregulated in the United States and has received far less public attention and policy discussion than other technologies that seek to exert control over genetic traits, such as germline gene editing via CRISPR. To better understand the public's views toward PGT-P, researchers conducted a prerecorded national survey experiment on attitudes toward PGT-P. The authors found that moral acceptability and willingness to use PGT-P were higher than those for germline gene editing. 

For the first time, researchers have watched human ‘organizer’ cells direct the formation of an embryo’s top, bottom, front and back. They did so by developing a technique that sidesteps restrictions on research with human embryos by grafting human cells onto chicken embryos. The method, published on 23 May in Nature1, could supplant the use of human embryos in some laboratory experiments.