RNA-Based Antipsoriatic Gene Therapy: An Updated Review Focusing on Evidence from Animal Models

Abstract

Psoriasis presents as a complex genetic skin disorder, characterized by the interaction between infiltrated immune cells and keratinocytes. Substantial progress has been made in understanding the molecular mechanisms of both coding and non-coding genes, which has positively impacted clinical treatment approaches. Despite extensive research into the genetic aspects of psoriasis pathogenesis, fully grasping its epigenetic component remains a challenging endeavor. In response to the pressing demand for innovative treatments to alleviate inflammatory skin disorders, various novel strategies are under consideration. These include gene therapy employing antisense nucleotides, silencing RNA complexes, stem cell therapy, and antibody-based therapy. There is a pressing requirement for a psoriasis-like animal model that replicates human psoriasis to facilitate early preclinical evaluations of these novel treatments. The authors conduct a comprehensive review of various gene therapy in different psoriasis-like animal models utilized in psoriasis research. The animals included in the list underwent skin treatments such as imiquimod application, as well as genetic and biologic injections, and the results of these interventions are detailed. Animal models play a crucial role in translating drug discoveries from the laboratory to clinical practice, and these models aid in improving the reproducibility and clinical applicability of preclinical data. Numerous animal models with characteristics similar to those of human psoriasis have proven to be useful in understanding the development of psoriasis. In this review, the article focuses on RNA-based gene therapy exploration in different types of psoriasis-like animal models to improve the treatment of psoriasis.

Keywords:

• psoriasis
• animal model
• gene therapy
• siRNA
• miRNA

Abbreviation

ASODN, antisense oligonucleotide; CARD14, caspase recruitment domain family member 14; CARM1, Coactivator-associated arginine methyltransferase 1; Cas9, CRISPR associated protein 9; Cdr1as, Cerebellar degeneration-related protein 1 antisense RNA; DDX58, DEAD (Asp-Glu-Ala-Asp) box polypeptide 58; DEFB4, Defensin Beta 4A; ELMO1, Engulfment And Cell Motility 1; ETS1, ETS Proto-Oncogene 1; FBXL19, F-box and leucine-rich repeat protein 19; FGFR2, fibroblast growth factor receptor 2; GWAS, genome-wide association studies; hBD-2, Human beta-defensin-2; HOTAIR, HOX Transcript Antisense RNA; IF3, initiation factor 3; IFIH1, IFIH1 interferon induced with helicase C domain 1; IFN, Interferon; IFNLR1, Interferon Lambda Receptor 1; IL, interleukin; IRAK1, interleukin-1 receptor-associated kinase 1; IRF4, IRF4 interferon regulatory factor 4; KLF4, Krüppel-like factor 4; KRT17, Keratin 17; LncRNA, long non-coding RNAs; MBD2, Methylated DNA binding domain protein 2; MDA5, melanoma differentiation-associated protein 5; MEG3, Maternally Expressed 3; miRNA, microRNA; NETs, neutrophil extracellular traps; NFkBIA, nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family pyrin domain containing 3; PDCD4, programmed cell death 4; Pp6fl/fl, loxP-flanked PP6 alleles; PPP6C, protein phosphatase 6 catalytic subunit; REL, REL Proto-Oncogene; RIG1, retinoic acid-inducible gene I; RNA, ribonucleic acid; RNF114, ring finger protein 114; RUNX3, RUNX family transcription factor 3; SECosomes, surfactant-ethanol-cholesterol-osomes; siRNA, small interfering RNA; SNPs, single-Nucleotide Polymorphisms; SOCS1, SOCS1 suppressor of cytokine signaling 1; SPRY1, sprouty homolog 1; STAT, Signal transducer and activator of transcription; TGF-β, Transforming growth factor beta; TINCR, Terminal differentiation-induced noncoding RNA; TLR, Toll-Like Receptors; TNF, tumor necrosis factor; TNFAIP3, Tumor necrosis factor, alpha-induced protein 3; TNFRSF9, TNF Receptor Superfamily Member 9; TRAF6, TNF receptor-associated factor 6; TSLP, thymic stromal lymphopoietin; TYK2, Tyrosine kinase 2; UBE2L3, Ubiquitin Conjugating Enzyme E2 L3;VEGF, vascular endothelial growth factor.

Disclosure

The authors declare no competing interests in this work.

Additional information

Funding

The authors are grateful for the financial support from Ministry of Science and Technology of Taiwan (MOST-110-2320-B-182-011-MY3), Chang Gung University of Science and Technology (ZRRPF6N0011) and Chi Mei Medical Center (110-CM-FJU-06). The authors also express their gratitude for the graphic design expertise provided by Jia-Yin Lin.