Citation: Kanu, G.A.; Parambath, J.B.M.; Abu Odeh, R.O.; Mohamed, A.A. Gold Nanoparticle-Mediated Gene Therapy. Cancers 2022, 14, 5366. https://doi.org/10.3390/ cancers14215366 Academic Editor: Olivier Cuvillier Received: 29 September 2022 Accepted: 28 October 2022 Published: 31 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Review Gold Nanoparticle-Mediated Gene Therapy Gayathri A. Kanu 1 , Javad B. M. Parambath 2,3 , Raed O. Abu Odeh 1, * and Ahmed A. Mohamed 2,3, * 1 Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates 2 Department of Chemistry, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates 3 Center for Advanced Materials Research, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates * Correspondence: rabuodeh@sharjah.ac.ae (R.O.A.O.); amohamed61@gmail.com (A.A.M.) Simple Summary: Successful gene therapy mainly depends on the fabrication of efficient and nontoxic carriers that can compact genetic materials and adequately deliver them to target cells. Nanoscale gold-mediated gene delivery systems have been considered a powerful tool for gene therapy because of their inherent potential of nontoxicity, high specificity, and therapeutic efficacy. Here, we summarize the updated progress in gene therapy by taking an edge on the unique properties of the gold nanoparticles. Distinct employed by these nano-carriers for gene-silencing and gene- editing are a great deal of optimism for the treatment of human fatal genetic disorders. From other published reviews on gold theranostics, this article discusses the recent advances of gold nanostructures in gene therapeutics for diseases caused by a single gene in humans. The promising advancements employed by these nano-carriers for gene-silencing and gene-editing are a great deal of optimism for the treatment of human fatal genetic disorders. Abstract: Gold nanoparticles (AuNPs) have gained increasing attention as novel drug-delivery nanostructures for the treatment of cancers, infections, inflammations, and other diseases and dis- orders. They are versatile in design, synthesis, modification, and functionalization. This has many advantages in terms of gene editing and gene silencing, and their application in genetic illnesses. The development of several techniques such as CRISPR/Cas9, TALEN, and ZFNs has raised hopes for the treatment of genetic abnormalities, although more focused experimentation is still needed. AuNPs, however, have been much more effective in trending research on this subject. In this review, we highlight recently well-developed advancements that are relevant to cutting-edge gene therapies, namely gene editing and gene silencing in diseases caused by a single gene in humans by taking an edge of the unique properties of the AuNPs, which will be an important outlook for future research. Keywords: CRISPR/Cas9 system; zinc finger nucleases; TALENs gene editing; RNA interference (RNAi); antisense oligonucleotides 1. Introduction Inorganic functional nanomaterials have emerged as reliable and adaptable nano scaffolds for gene delivery [1,2]. The synthesis of numerous primary proteins in microbes and living cells is the focus of cutting-edge recombinant techniques that have replaced outdated methods and the current trends in bio-nanotechnology. For example, “The Human Genome Project” and its developments in molecular genetics in high-throughput techniques have enabled us to decipher the genetic background of numerous diseases and discover novel therapeutic targets [3]. More focus has been placed on nanomedicine, which has enormous future potential to improve nucleic acid-based treatments, such as gene editing, gene silencing, and viral vectors. These have the potential to significantly advance the treatment of cancer and genetic diseases, such as acute immunodeficiency and Parkinsonism [4]. Cancers 2022, 14, 5366. https://doi.org/10.3390/cancers14215366 https://www.mdpi.com/journal/cancers