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Gene & Protein in Disease                                                  Enhancing fertility with CRISPR



            with a particularly promising application in  in vivo   with methods such as viral vectors, DNA plasmid vectors,
            treatment for genetic disorders in humans.  Gene therapy   electroporation,  and  microinjections, each having
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            shows potential in addressing gynecological disorders,   drawbacks ranging from cytotoxicity to the permanent
            including ovarian, cervical, and endometrial cancer,   permeabilization of plasma membranes. 47
            uterine  leiomyomas,  endometriosis, and complications
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            with placental and embryo implantation.  Research   4.1. Concerns over designer babies and eugenics
            on premature ovarian insufficiency explores genetic   Genome  editing  in  germlines  holds  the  potential  to
            therapy  targets  such as  the follicle-stimulating  hormone   eliminate heritable genetic disorders and enhance human
            receptor, apoptosis management alterations, Sal-like four   health significantly. However, along with these potential
            gene polymorphisms, and deficiencies in thymulin or   benefits, there are accompanying risks and disadvantages,
            basonuclin-1. 91                                   particularly if not used and regulated properly. A major
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              CRISPR research extends to comprehending and     concern is the concept of “designer babies”,  where the
            treating various diseases, including reproductive system   use of genome editing in human embryos may usher in
            cancers. A synthetic technique for in vivo CRISPR-mediated   a new era of “new eugenics,” potentially widening social
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            activation of tumor suppressor genes has shown promise   disparities.  The contentious issue of creating genetically
            in  reducing  tumor  burden.   CRISPR-Cas9  gene  editing   modified children using CRISPR technology raises ethical
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            exhibits potential in treating gynecological disorders such   questions about the manipulation of infants, commonly
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            as cervical, ovarian, and endometrial cancer.  Studies on   referred to as designer babies.  Bioethical and social
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            endometrial cancer reveal the preventive effects of cationic   concerns surrounding  genome  editing  in germline cells
            microbubbles containing paclitaxel and CRISPR/Cas9   primarily stem from these ethical dilemmas. Another
                                                               significant concern involves the potential application
            plasmids in a mouse xenograft model.  Animal models   of CRISPR technology in eugenics,  where it could be
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            of endometrioid carcinoma and high-grade serous    employed to alter human attributes to create “superior”
            carcinoma have been developed using CRISPR/Cas9-   individuals or eliminate “undesirable” traits. This
            mediated somatic gene editing.  Despite the effectiveness   application raises ethical concerns due to the possibility of
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            of  CRISPR-Cas9  in  treating  gynecological  malignancies,   unforeseen consequences, discrimination, and the loss of
            further research is needed to address potential drawbacks,   genetic diversity. 105-107
            such as off-target effects, before widespread clinical
            application.  Although gene therapy for reproductive   4.2. Regulation and oversight of CRISPR applications
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            disorders is in its early stages, promising results suggest its   in reproductive biology
            potential role in future treatments. 90,91
                                                               Regulations and monitoring mechanisms for CRISPR
              In conclusion, CRISPR technology holds promise for   applications in reproductive biology are currently being
            enhancing both male and female reproductive health, as   developed by national and international regulatory bodies.
            evidenced by trials on NHPs and other animal models.   These guidelines aim to address safety criteria, as well
            However, ethical considerations must be carefully   as social and ethical concerns associated with germline
            addressed in the application of this technology.   genome editing for reproductive purposes.  Regulations
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                                                               governing the use of CRISPR in reproductive biology vary
            4. Risks and limitations of CRISPR                 by  country  and  are  continually  evolving.  One  notable
            technology                                         concern  is  the  potential  for  dual-use  research,  where

            Despite the apparent advantages of CRISPR/Cas technology,   CRISPR technology might be misapplied or intentionally
            several downsides require resolution. Particularly, its   developed for harmful purposes. 109
            application in human embryos raises medical and ethical   Historically, both international and state legislation
            concerns due  to the  potential unforeseen consequences,   has restricted genome editing, largely due to ethical
            such as off-target mutations, which may be inherited by   considerations. However, there has been notable progress
            subsequent generations.  Off-target effects, characterized   in reconsidering these laws. A recent consensus statement
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            by the unintended cleavage of DNA sequences similar   issued  after  the  International  Summit  on  Gene  Editing
            to  the  target  sequence,  pose  a  significant  challenge. 98,99    in Washington, D.C., emphasizes the discouragement of
            Another limitation is the low efficiency of multigene   germline editing, stating that it should only be considered
            editing, which concerns the scientific community.    in cases where couples are affected by diseases involving a
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            In addition, the CRISPR/Cas system is associated with   dominant disease-causing allele in a homozygous state or
            cytotoxicity and immunotoxicity.  Moreover, the delivery   rare recessive homozygous mutations considered lethal.
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            of CRISPR components to the desired site is constrained,   There is a pressing need for a comprehensive and impartial
            Volume 3 Issue 1 (2024)                         8                        https://doi.org/10.36922/gpd.2701
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