ABSTRACT
The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.
Subject(s)
CRISPR-Cas Systems , Gene Editing , Genetic Diseases, Inborn , Genetic Therapy , Rare Diseases , Humans , Rare Diseases/genetics , Rare Diseases/therapy , Gene Editing/methods , Genetic Therapy/methods , Genetic Diseases, Inborn/therapy , Genetic Diseases, Inborn/genetics , Oligonucleotides, Antisense/therapeutic use , RNA, Small Interfering/therapeutic use , RNA, Small Interfering/genetics , MicroRNAs/genetics , Aptamers, Nucleotide/therapeutic useABSTRACT
Dengue is potentially a life-threatening arthropod-borne viral infection for which there are no known therapeutic agents till date. Early stage diagnosis of dengue infection is still lacking. Diagnosis is only made after severe manifestations and later stages of infection. Timely prognosis can prevent dengue related mortalities. The nucleic acid-based therapy has potential to emerge as a promising approach for early diagnosis and treatment of this viral infection. Many studies have been carried out suggested the regulatory role of ncRNAs thereby revealing the importance of protein-RNA and RNA-RNA interactions during infection. Various regulatory RNAs are either expressed by mammalian cells or generated by viral RNA have reported to play important roles in viral life cycle including dengue virus. Thus exploring host-virus interaction will pave the novel path for understanding the pathophysiology of febrile infection in dengue. Rapid advances in sequencing techniques along with significant developments in the field of RNA studies has made RNA therapeutics as one of the promising approaches as antiviral targets. The idea of RNA based therapies has been greatly backed by a Hepatitis C virus drug, Miravirsen which has successfully completed phase II clinical trial. In the present review, we will discuss the implications of different non-coding RNAs in dengue infection. Differential expression of small ncRNA may serve as a reliable biomarker of disease severity during different stages of infection and can also play regulatory roles in disease progression.
