Adverse Drug Reactions and Toxicity of the Food and Drug Administration–Approved Antisense Oligonucleotide Drugs

Alhamadani, Feryal; Zhang, Kristy; Parikh, Rajvi; Wu, Hao; Rasmussen, Theodore P.; Bahal, Raman; Zhong, Xiao‐bo; Manautou, José E.

doi:10.1124/dmd.121.000418

Cited by 60 publications

(42 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More than 50 ASO drugs are in clinical studies. Fomivirsen is the first ASO drug approved by the FDA for the treatment of cytomegalovirus-infected retinitis (CMV) in HIV patients [ 49 ]. Due to the development of highly active antiretroviral therapy (HAART), the number of CMV cases has decreased dramatically.…”

Section: Nucleic Acid Drugsmentioning

confidence: 99%

Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy

et al. 2023

View full text Add to dashboard Cite

Gene therapy, as an emerging therapeutic approach, has shown remarkable advantages in the treatment of some major diseases. With the deepening of genomics research, people have gradually realized that the emergence and development of many diseases are related to genetic abnormalities. Therefore, nucleic acid drugs are gradually becoming a new boon in the treatment of diseases (especially tumors and genetic diseases). It is conservatively estimated that the global market of nucleic acid drugs will exceed $20 billion by 2025. They are simple in design, mature in synthesis, and have good biocompatibility. However, the shortcomings of nucleic acid, such as poor stability, low bioavailability, and poor targeting, greatly limit the clinical application of nucleic acid. Liposome nanoparticles can wrap nucleic acid drugs in internal cavities, increase the stability of nucleic acid and prolong blood circulation time, thus improving the transfection efficiency. This review focuses on the recent advances and potential applications of liposome nanoparticles modified with nucleic acid drugs (DNA, RNA, and ASO) and different chemical molecules (peptides, polymers, dendrimers, fluorescent molecules, magnetic nanoparticles, and receptor targeting molecules). The ability of liposome nanoparticles to deliver nucleic acid drugs is also discussed in detail. We hope that this review will help researchers design safer and more efficient liposome nanoparticles, and accelerate the application of nucleic acid drugs in gene therapy.

show abstract

Section: Nucleic Acid Drugsmentioning

confidence: 99%

Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Some of the oligonucleotide drug-treated patients developed thrombocytopenia. Golodirsen-treated patients exhibited hypersensitivity reactions, including rash and skin exfoliation (Alhamadani et al, 2022).…”

Section: Clinical Experience With Rnatargeting Therapiesmentioning

confidence: 99%

Natural antisense transcripts as drug targets

Khorkova

Stahl

Joji

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

The recent discovery of vast non-coding RNA-based regulatory networks that can be easily modulated by nucleic acid-based drugs has opened numerous new therapeutic possibilities. Long non-coding RNA, and natural antisense transcripts (NATs) in particular, play a significant role in networks that involve a wide variety of disease-relevant biological mechanisms such as transcription, splicing, translation, mRNA degradation and others. Currently, significant efforts are dedicated to harnessing these newly emerging NAT-mediated biological mechanisms for therapeutic purposes. This review will highlight the recent clinical and pre-clinical developments in this field and survey the advances in nucleic acid-based drug technologies that make these developments possible.

show abstract

“…As most ASOs accumulate in high concentrations in the liver and kidneys, varying levels of toxicity in these organs have been reported with some sequence and chemistry combinations, especially at higher doses than those used in a clinical setting [ 58 , 163 ]. Non-specific interactions of polyanionic ASOs with proteins are thought to contribute to hepatic degeneration [ 164 ].…”

Section: Safety and Tolerability Of Dmpk -Targetin...mentioning

confidence: 99%

Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1

Serres-Bérard

Benichou

Jauvin

et al. 2022

IJMS

View full text Add to dashboard Cite

Myotonic dystrophy type 1 (DM1) is a dominant genetic disease in which the expansion of long CTG trinucleotides in the 3′ UTR of the myotonic dystrophy protein kinase (DMPK) gene results in toxic RNA gain-of-function and gene mis-splicing affecting mainly the muscles, the heart, and the brain. The CUG-expanded transcripts are a suitable target for the development of antisense oligonucleotide (ASO) therapies. Various chemical modifications of the sugar-phosphate backbone have been reported to significantly enhance the affinity of ASOs for RNA and their resistance to nucleases, making it possible to reverse DM1-like symptoms following systemic administration in different transgenic mouse models. However, specific tissue delivery remains to be improved to achieve significant clinical outcomes in humans. Several strategies, including ASO conjugation to cell-penetrating peptides, fatty acids, or monoclonal antibodies, have recently been shown to improve potency in muscle and cardiac tissues in mice. Moreover, intrathecal administration of ASOs may be an advantageous complementary administration route to bypass the blood-brain barrier and correct defects of the central nervous system in DM1. This review describes the evolution of the chemical design of antisense oligonucleotides targeting CUG-expanded mRNAs and how recent advances in the field may be game-changing by forwarding laboratory findings into clinical research and treatments for DM1 and other microsatellite diseases.

show abstract

Adverse Drug Reactions and Toxicity of the Food and Drug Administration–Approved Antisense Oligonucleotide Drugs

Cited by 60 publications

References 58 publications

Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy

Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy

Natural antisense transcripts as drug targets

Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1

Contact Info

Product

Resources

About