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to DIYbio, jcline
Science.
Correction of a pathogenic gene mutation in human embryos
Nature
doi:10.1038/nature23305
""..
the IRAP recommended allowing this research “with significant oversight and continued dialogue, the use of gene correction technologies in human embryos for the purpose of answering basic science questions needed to evaluate germline gene correction prior to the use in human models” ""
--quote--
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.
....
Regulations for research on human gametes and embryos
The regulatory framework surrounding the use of human gametes and embryos for this research was based on the guidelines set by the Oregon Health & Science University (OHSU) Stem Cell Research Oversight Committee (OSCRO). In 2008, OSCRO established policy and procedural guidelines formally defining the use of human embryos and their derivatives at OHSU, informed by the National Academy of Sciences’ Guidelines. These policies and guidelines permitted the procurement of gametes and embryos for research purposes, the creation of human embryos specifically for research, genetic manipulation of human gametes and embryos, creation of human embryonic stem cell lines and molecular analyses. Together, OSCRO and the OHSU Institutional Review Board (IRB) worked concurrently to review and monitor applications for research studies involving human embryos at OHSU.
Human embryo and embryonic stem cell research policies and principles at OHSU were vetted over the course of a decade informed by the NAS guidelines, and subsequently affirmed by new guidelines released in 2015 by the Hinxton Group, the International Society for Stem Cell Research (ISSCR), and 2017 recommendations by the NAS and National Academy of Medicine joint panel on human genome editing.
As part of the review process, OHSU convened additional ad hoc committees to evaluate the scientific merit and ethical justification of the proposed study: the OHSU Innovative Research Advisory Panel (IRAP) and a Scientific Review Committee (SRC). Members of both committees were independent and their names were kept confidential from the research team; OHSU Research Integrity supervised all committee meetings, documentation, and formal recommendations.
Ethical review
While international discussions were in their infancy, the OHSU Innovative Research Advisory Panel (IRAP) Committee was tasked with deliberating ethical considerations related to using gene correction technology in human embryos for basic research at OHSU. The committee was composed of eleven members from internal and external sources: a lay member, a clinical ObGyn physician, three bioethicists, an OHSU Institutional Ethics committee member, three former OSCRO members, a clinical geneticist, and a clinician. Upon completion of the review, the IRAP recommended allowing this research “with significant oversight and continued dialogue, the use of gene correction technologies in human embryos for the purpose of answering basic science questions needed to evaluate germline gene correction prior to the use in human models,” at OHSU.
