Recent Advances and Prospects in RNA Drug Development

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12284 - 12284

Опубликована: Ноя. 15, 2024

RNA therapeutics have undergone remarkable evolution since their inception in the late 1970s, revolutionizing medicine by offering new possibilities for treating previously intractable diseases. The field encompasses various modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger (mRNAs), each with unique mechanisms applications. foundation was laid 1978 discovery that synthetic could inhibit viral replication, followed pivotal developments such as interference's 1998. COVID-19 pandemic marked a crucial turning point, demonstrating potential of mRNA vaccines accelerating interest RNA-based approaches. However, significant challenges remain, stability issues, delivery to target tissues, off-target effects, immunogenicity concerns. Recent advancements chemical modifications, systems, integration AI technologies are addressing these challenges. has seen notable successes, approved treatments spinal muscular atrophy hereditary transthyretin-mediated amyloidosis. Looking ahead, show promise personalized approaches, particularly genetic disorders cancer. continued this field, driven technological innovations deeper understanding biology, suggests transformative impact on future medical treatments. purpose review is provide comprehensive overview evolution, current state, prospects therapeutics.

Язык: Английский

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Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4263 - 4263

Опубликована: Апрель 12, 2024

In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in treatment β-thalassemia or Sickle-cell disease (SCD). This field investigation is relevant, since it expected to help clinicians select appropriate drug correct dosage for each patient. We first search DNA polymorphisms associated with a high expression γ-globin genes identified using GWAS CRISPR-based gene editing approaches. then validated HbF production (including, but not limited HBG2 XmnI polymorphism those related BCL11A, MYB, KLF-1, LYAR genes). The microRNAs involved regulation was also context pharmacomiRNomics. Then, fetal hemoglobin inducers (hydroxyurea, butyrate analogues, thalidomide, sirolimus), iron chelators, analgesics pain management SCD patients were considered. Finally, discuss current clinical trials, as well international research networks focusing issues hematological diseases.

Язык: Английский

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RNA Structure: Past, Future, and Gene Therapy Applications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 110 - 110

Опубликована: Дек. 26, 2024

First believed to be a simple intermediary between the information encoded in deoxyribonucleic acid and that functionally displayed proteins, ribonucleic (RNA) is now known have many functions through its abundance intricate, ubiquitous, diverse, dynamic structure. About 70–90% of human genome transcribed into protein-coding noncoding RNAs as main determinants along with regulatory sequences cellular populational biological diversity. From nucleotide sequence or primary structure, Watson–Crick pairing self-folding secondary compaction via longer distance non-Watson–Crick interactions tertiary RNA other biopolymers quaternary metabolites biomolecules quinary structure plays critical role RNA’s lifecycle from transcription decay processes. In contrast success 3-dimensional protein prediction using AlphaFold, beyond structures remains challenging. However, approaches involving machine learning artificial intelligence, sequencing modifications, structural analyses at single-cell intact tissue levels, among others, provide an optimistic outlook for continued development refinement RNA-based applications. Here, we highlight those gene therapy.

Язык: Английский

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Exosomes as novel nanocarriers for cancer therapy

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 101, С. 106262 - 106262

Опубликована: Окт. 9, 2024

Язык: Английский

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