Review
Genetics & Heredity
Ying-Xuan Xie, Wen-Qi Lv, Yi-Kun Chen, Shunyan Hong, Xiang-Ping Yao, Wan-Jin Chen, Miao Zhao
Summary: Neurogenetic diseases are neurological conditions with a genetic cause that are mostly incurable. Gene therapy approaches such as viral vectors delivery, antisense oligonucleotides, and gene editing have shown promising therapeutic effects in treating neurogenetic diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Chemistry, Analytical
Toshitsugu Fujita, Shoko Nagata, Hodaka Fujii
Summary: Blocking PCR is a method to selectively inhibit the amplification of wild-type DNA while amplifying mutated DNA by using a nucleotide sequence complementary to a blocker. Our study demonstrates that an oligoribonucleotide (ORN) can effectively suppress the extension of target DNA by Taq DNA polymerases. This method has been successfully applied for real-time ORNi-PCR and one-step real-time reverse transcriptionORNi-PCR to detect single-nucleotide mutations in DNA and RNA in a sequence-specific manner, providing technical insights for further improvement of blocking PCR.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Nitin A. Patil, Varsha J. Thombare, Rong Li, Xiaoji He, Jing Lu, Heidi H. Yu, Hasini Wickremasinghe, Kavya Pamulapati, Mohammad A. K. Azad, Tony Velkov, Kade D. Roberts, Jian Li
Summary: Peptide-Peptide Nucleic Acid (PNA) conjugates have shown potential in developing novel antisense antimicrobials. The efficiency of Cys-CINA conjugation was investigated for synthesizing peptide-PNA conjugates, which demonstrated improved antimicrobial activity against multidrug-resistant Gram-negative bacteria.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xue-hai Liang, Joshua G. Nichols, Dario Tejera, Stanley T. Crooke
Summary: Studies have shown that the distribution and activity of PS-ASO in cells are affected by endosome movement and perinuclear positioning. PS-ASO moves linearly along microtubules and covers substantial distances in late endosomes, while perinuclear positioning is necessary for efficient release of PS-ASO.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Chengxi Li, Alex J. Callahan, Kruttika S. Phadke, Bryan Bellaire, Charlotte E. Farquhar, Genwei Zhang, Carly K. Schissel, Alexander J. Mijalis, Nina Hartrampf, Andrei Loas, David E. Verhoeven, Bradley L. Pentelute
Summary: This study reports an efficient technology that utilizes a fully automated fast-flow instrument to manufacture cell-penetrating peptide-conjugated peptide nucleic acids (PPNAs), which improves cellular uptake. The synthesized PPNAs showed improved activity in splice-correction and antiviral assays. This technology has the potential to be used for further investigation of PPNA candidates as antiviral agents.
ACS CENTRAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Naim Alkhouri, Samer Gawrieh
Summary: Therapeutic oligonucleotides have shown promise in silencing undruggable targets, particularly in treating metabolic liver diseases. The liver offers numerous susceptible molecular targets for modulation via therapeutic oligonucleotides, which align well with the progress in precision medicine.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Article
Medicine, Research & Experimental
Katelyn A. Doxtader Lacy, Xue-hai Liang, Lingdi Zhang, Stanley T. Crooke
Summary: Phosphorothioate modified antisense oligonucleotides (PS-ASOs) can reduce gene expression by binding to target RNAs and being cleaved by RNase H1. However, the effects of RNA modifications on PS-ASO binding and RNase H1 cleavage activity are not well understood. In this study, we investigated the effects of three different RNA modifications on PS-ASO binding and antisense activity, and found that these modifications can not only directly affect PS-ASO hybridization and RNase H1 activity, but also alter the RNA structure, potentially affecting PS-ASO accessibility in a cellular context.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Cell Biology
Charles Holjencin, Andrew Jakymiw
Summary: This review discusses the delivery systems for miRNA-based cancer therapy. MiRNA plays essential roles in regulating physiological processes and cancer pathologies. However, the use of nucleic acid-based delivery faces many obstacles. The review focuses on nonviral nanotechnology-based platforms, including lipid, polymer, inorganic, and extracellular vesicle-based strategies, and also highlights peptide carriers as a promising delivery platform.
Article
Multidisciplinary Sciences
Chikako Senju, Yuka Nakazawa, Taichi Oso, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, Tomoo Ogi
Summary: Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by photosensitivity and a high risk of skin tumors due to DNA repair deficiency. This study identified two deep intronic mutations in the ERCC4/XPF gene in 17 cases of XP-F, a rare subtype of XP. These mutations result in reduced gene expression and early-onset skin cancers, highlighting the need for attention to these variants. Additionally, antisense oligonucleotides designed for these mutations can restore DNA repair capacity, suggesting potential therapeutic targets for XP-F.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Pharmacology & Pharmacy
Mohadeseh Dastpeyman, Ramin Sharifi, Azin Amin, John A. Karas, Brittany Cuic, Yijun Pan, Joseph A. Nicolazzo, Bradley J. Turner, Fazel Shabanpoor
Summary: This study demonstrates that integrating endosomal escape domains with CPPs can improve the intracellular delivery efficiency of ASOs, and enhance the efficiency of BBB-permeability and CNS activity of systemically administered ASOs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Pharmacology & Pharmacy
Vasanti Suvarna, Kajal Deshmukh, Manikanta Murahari
Summary: Alpha-synuclein plays a key role in neurodegenerative diseases, especially Parkinson's disease. Recent advances in oligonucleotide chemistry have shown potential in targeting alpha-synuclein for therapeutic intervention in neurodegenerative diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Organic
Ashwani Sharma, Shahaji H. More, Krishna N. Ganesh
Summary: The study introduces a novel cationic PNA, dapPNA, which demonstrates that the electrostatic attraction between cationic dapPNA and negatively charged DNA can enhance the stability of PNA : DNA complexes, overcoming unfavorable stereochemical effects. Additionally, the synthesis of two different PNA backbones derived from a single PNA monomer expands the repertoire of pyrrolidine-based PNA analogues.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Nanoscience & Nanotechnology
Huiying Xu, Chong Liao, Shifu Liang, Bang-Ce Ye
Summary: Exosomes are natural delivery vehicles with features like low immunogenicity, excellent biocompatibility, and migration capability. This study developed a novel peptide-equipped exosomes platform that can improve cellular uptake efficiency and deliver nucleic acids effectively, showing potential for personalized cancer medicine.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Alireza Japoni Nejad, Nader Shahrokhi, Peter E. Nielsen
Summary: In this study, a series of PNA-BPP conjugates targeting CRAB strains were designed and synthesized. These compounds demonstrated potent antimicrobial activity against CRAB, exhibiting complete growth inhibition at 1-2x MIC and sensitivity in 12 isolates. Additionally, the conjugates showed no bacterial membrane disruption activity and no cellular toxicity in HepG2 cells, indicating potential as precision designer antibiotics for specific treatment of CRAB infections.
Article
Biochemistry & Molecular Biology
Greta Linden, Harshavardhan Janga, Matthias Franz, Andrea Nist, Thorsten Stiewe, Bernd Schmeck, Olalla Vazquez, Leon N. Schulte
Summary: This study successfully utilized cell penetrating peptide chemistry to enable the loss-of-function phenotyping of regulatory RNAs in primary human blood-derived cells. The results showed that PNA-R8 was effective at a lower concentration than previously believed and highlighted the important role of microRNA-155 in fine control of human phagocyte immunity.