Using CRISPR-Cas9 In Human Fetuses to Prevent Trisomy 16 and Trisomy 22 Induced Miscarriages

Abstract

About 50% of abortions have been found to be caused by aneuploidy, roughly 60% of which are trisomy. The most common trisomy occurs on chromosome 16, 21, and 22. However, trisomy 21 (also called Down Syndrome) is viable in about 57% of cases, while trisomy 16 and 22 result in miscarriage in nearly every pregnancy. Thus, additional therapies and treatments must be explored, especially through quickly advancing techniques such as gene editing. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) combined with the cleaving endonuclease CRISPR-associated protein (Cas9) harbors potential for targeted chromosome deletion, possibly increasing the chance of survival in fetuses with trisomy 16 or 22. However, the risks and safety benefits during genetic diagnosing and potential treatment of the fetus should also be considered. Successfully demonstrated approaches of editing or eliminating extraneous chromosomes in studies of both animal models and lab-cultured human embryos will be discussed. In particular, this paper will examine possible gene editing approaches such as elimination of entire chromosomes, large-scale deletions, and chromosomal truncations to target trisomy. In order to determine the efficacy of these approaches in trisomy, the use of CRISPR-Cas9 to specifically treat trisomy via autosomal deletion and counter-selection markers will be deliberated. Delivery methods for the in-utero therapy includes viral techniques such as retroviruses and adeno-associated vectors (AAVs) as well as non-viral techniques like electroporation and nanoparticles. This paper will propose hypothetical treatments for CRISPR-Cas9 in human embryos to target trisomy 16 and 22 while also examining the bioethical implications of doing so.