Health Canada's current interpretation is that it would apply to any attempt at gene editing in the early human embryo, even if the embryos were only studied in culture. OpenUrlCrossRefPubMed Accessed October 10, 2019. By continuing you agree to the use of cookies. Their report titled “Genome editing: an ethical … Get monthly alerts when a new issue is published. Although technical and safety issues suggest that this approach is far from clinical application, gene editing as a research tool is moving forward in human embryos, non-human primates and in stem cell-derived embryoids. ↵ It has the potential to radically transform many industries, including medicine, agriculture and ecology. Random integration of donor vector (illegitimate recombination at a spontaneous or induced DSB) leading to local gene inactivation, dysregulation, Random integration of nuclease expression vector (illegitimate recombination at a spontaneous or induced DSB) leading to persistent nuclease expression, Delivery related (transfection, microinjection, electroporation, viral vector), Induction of inflammatory responses to vector components, Delivery device related (needles, catheters, transplants, stereotactic, electroporation in vivo), Loss of stem cell activity and/or engraftment activity; impaired differentiation/function; inherent genome instability during culture, Cannot be used on populations of cells because of sensitivity, Bioinformatics based: use computational tools to predict off-target sites and then deep sequence predicted sites to assess whether insertions/deletions are being created, Many currently available algorithms and sequencing platforms make this easily available, Prediction algorithms have not routinely identified all of the off-target sites that have been found using other methods, Only assesses a small number of cells (20-50). We use cookies to help provide and enhance our service and tailor content and ads. 18, 700-708. doi:10.1038/ncb3347 Although ethical, safety, and legal considerations are important in the innovation process, the expertise of patent examiners solely concerns the technical merits of an invention. Published by The Company of Biologists Ltd It is unsurprising that genome editing for human reproduction is listed as requiring urgent attention. No further action would be taken by the USPTO. The resulting gene-corrected embryo could be implanted in utero for development to a live birth with every cell containing the genome edit. (a) Whoever invents or discovers any useful process, machine, manufacture, or composition of matter, or any useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. First, as a basic research tool for use in human cells or embryos to help understand normal development, model human disease and develop new treatments. The third, and perhaps most problematic, practical limitation is that one cannot assure that a harmful unintended heritable modification does not occur in the context of an intentional germ line editing procedure, when there is no capacity for characterization of a modified germ cell postprocedure. These studies are Those in favor of the proposed changes to Section 101 of Title 35 of the US Code assert that changes are necessary to create order out of the labyrinth of case law that currently exists. (k) The term “useful” means any invention or discovery that provides specific and practical utility in any field of technology through human intervention. Revised January 2018. Although important information can be gained using these assays in surrogate cell types, such as transformed cell lines, which can then guide how to improve the relative specificity, the key assays need to be performed in the therapeutic cell type of interest. Generation of a nonhuman primate model of severe combined immunodeficiency using highly efficient genome editing. Zhou, Q., Wang, M., Yuan, Y., Wang, X., Fu, R., Wan, H., Xie, M., Liu, M., Guo, X., Zheng, Y. et al. OpenUrlCrossRefPubMed, Human lung development: recent progress and new challenges. 6,630,507B1 (filed February 2, 2001) (issued October 7, 2003). 6 In November 2018, He Jiankui announced the birth of twin girls with a modified version of the CCR5 gene, 7 an alteration that could confer resistance to HIV infection. Thus, safe in vivo strategies should be designed such that the duration of nuclease expression is limited to minimize the exposure and potential genome modification of both target cells and nontarget cells. (2017). Functional oocytes and spermatids have also been produced from mouse embryonic stem cells (Hikabe et al., 2016; Zhou et al., 2016), raising the future possibility of generating oocyte or sperm progenitors from human pluripotent stem cells. The Nuffield Council of Bioethics released a report last Friday outlining the key ethical issues raised by genome editing technologies. Carolyn Riley Chapman, PhD, MS and Arthur L. Caplan, PhD, https://news.berkeley.edu/2019/07/16/eighth-crispr-patent-issued-by-u-s-seven-more-soon-to-come/, https://www.who.int/news-room/detail/26-07-2019-statement-on-governance-and-oversight-of-human-genome-editing, https://www.uspto.gov/web/offices/pac/mpep/index.html. Shao, Y., Taniguchi, K., Townshend, R. F., Miki, T., Gumucio, D. L. and Fu, J. This act states, “Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.”18 In practice, if a patent application disclosed and claimed a nuclear weapon or a human being, the USPTO would return the application, including an objection stating that the application was directed to nonstatutory subject matter. OpenUrlAbstract/FREE Full Text (2018). Moreover, it is currently easier to limit the duration of the nuclease expression in an ex vivo approach, such as by delivering the nuclease as protein or messenger RNA (mRNA), which not only limits the potential immune response but also limits the duration of exposure of the genome to a DSB-creating agent. Therefore, sequencing-based methods of analysis should be complemented by functional methods of assessing genotoxicity (Table 3). A global observatory for gene editing. If a patent examiner determines that the subject matter of a patent application fails to meet the standard set forth in Section 101 of Title 35 of the US Code, the patent application will be objected to and returned to the applicant. For example, despite the fact that cannabis and cannabis-derived products have been and still are illegal to possess or sell under the Controlled Substances Act,15 the USPTO has issued hundreds of patents relating to cannabis and cannabis-related products since the 1940s. Why Are Biosimilars Not Living up to Their Promise in the US? Consequently, development of ethical and regulatory frameworks that ensure their safe and effective use is an increasingly important consideration. Given these caveats on the lack of validated assays, it might be prudent in some of the first genome-editing clinical trials to demonstrate at a minimum that the production of DSBs is not detectable in genes that are associated with human cancers by whichever assay is used. Tewary, M., Ostblom, J., Prochazka, L., Zulueta-Coarasa, T., Shakiba, N., Fernandez-Gonzalez, R. and Zandstra, P. W. (2017). Despite the widespread prevalence of human in vitro fertilization as a means of aiding infertile couples, we still know very little about the molecular events of preimplantation development, implantation and early placental formation in humans. In terms of human germline-competent gene editing, there have been several additional studies demonstrating feasibility of gene correction in human diploid zygotes (Ma et al., 2017; Tang et al., 2017), as well as the demonstration that new base editing tools can be applied to human embryos to generate specific nucleotide alterations (Liang et al., 2017). Parallel assembly of actin and tropomyosin, but not myosin II, during de novo actin filament formation in live mice, Development and dynamics of cell polarity at a glance. The use of genome-editing technologies to modify various types of blood cells, including hematopoietic stem cells, has emerged as an important field of therapeutic development for hematopoietic disease. Further development in 3D can produce structures with morphological resemblance to the postimplantation amniotic sac (Shahbazi et al., 2017; Shao et al., 2017). In re Watson, 517 F.2d 465, 474-76, 186 USPQ 11, 19 (CCPA 1975) (stating that it is not the province of the Patent Office to determine, under section 101, whether drugs are safe). The precision of GE, combined with its ease of use and rapid development, is putting pressure on our current regulations. Footnotes Although advisory groups like the World Health Organization question whether certain forms of gene editing should be permitted, the US Patent Office routinely issues patents protecting this technology. She is also registered to practice before the United States Patent and Trademark Office. A member of the State Bar of Wisconsin and the Virginia State Bar, she earned a JD from Marquette University Law School and an MA in bioethics from the Medical College of Wisconsin. Although advisory groups like the World Health Organization question whether certain forms of gene editing should be permitted, the US Patent Office routinely issues patents protecting this technology. Protein Cell 6, 363-372. doi:10.1007/s13238-015-0153-5 OpenUrlCrossRef National Institutes of Health. Delivering the nuclease as mRNA or protein, either for in vivo or ex vivo approaches, would obviate that potential risk for the nuclease. All Rights Reserved. (2015). Like all gene-therapy approaches, a safety evaluation of the genetically modified cell phenotype is critical. Genome editing in livestock presents less complex ethical issues than in human reproduction. Another use of genome edited animals discussed by the Nuffield Report is in xenotransplantation. A proof of principle study used CRISPR-Cas9 to correct a genetic mutation causing cataracts in mouse spermatogonial stem cells and demonstrated transmission of the corrected allele to the next generation after intracytoplasmic sperm injection into mouse eggs (Wu et al., 2015).