Article
Biochemistry & Molecular Biology
Matthew L. Hammill, Kouta Tsubaki, Yuwei Wang, Golam Islam, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
Summary: We report the synthesis of an ortho-functionalized tetrafluorinated azobenzene phosphoramidite for site-specific incorporation into RNA. The ortho-functionalized tetrafluorinated azobenzene is embedded in the antisense strand of an siRNA duplex to form a modified siRNA. In cell culture, the modified siRNA can be reversibly controlled through photoconversion.
Article
Chemistry, Multidisciplinary
Melanie Walther, Waldemar Kipke, Raul Renken, Anne Staubitz
Summary: This study presents a novel method for stannylation and borylation of different positions of diazocines, which are azobenzene derived macrocyclic photoswitches with well resolved photostationary states. The results demonstrate their successful use in Stille cross-coupling and Suzuki cross-coupling reactions with organic bromides, achieving high yields.
Article
Chemistry, Multidisciplinary
Tingting Zheng, Jielin Fu, Qin Xiong, Xin Shen, Baolin Li, Xiaohu Zhao, Zhipeng Yu
Summary: We present the genetic incorporation of DBDAA isomers into proteins using two evolved Methanosarcina mazei pyrrolysine tRNA synthetases, with the ability to tune enzymatic activity via cucurbit[7]uril host-guest recognition under either dark or 405 nm photo-stimulation.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Sampreeth Thayyil, Yukinori Nishigami, Md Jahirul Islam, P. K. Hashim, Ken'ya Furuta, Kazuhiro Oiwa, Jian Yu, Min Yao, Toshiyuki Nakagaki, Nobuyuki Tamaoki
Summary: In this study, we developed azobenzene-based photoswitchable ATP antagonists to control the activity of motor proteins cytoplasmic and axonemal dyneins. Our ATP antagonists showed reversible photoswitching of cytoplasmic dynein activity and regulated axonemal dynein motor activity in a force generation model.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Si-Yuan Yu, Yi-Fan Ruan, Yi-Li Liu, De-Man Han, Hong Zhou, Wei-Wei Zhao, Dechen Jiang, Jing-Juan Xu, Hong-Yuan Chen
Summary: The study introduces a photocontrolled nanopipette capable of probing cellular ATP gradient at single-cell level with high sensitivity, selectivity, and reversibility, utilizing ATP-specific azobenzene-incorporated DNA aptamer strands for sensible transduction of variable nanopore size by ionic currents. The photoisomerized conformational change ensures noninvasive regeneration and repeated detection, allowing inducement and inhibition of cellular ATP to be probed.
Article
Engineering, Biomedical
Martijn J. W. Evers, Simonides van de Wakker, Ellis M. de Groot, Olivier G. de Jong, Jerney J. J. Gitz-Francois, Cor S. Seinen, Joost P. G. Sluijter, Raymond M. Schiffelers, Pieter Vader
Summary: EV-liposome hybrid nanoparticles have been investigated as a potential siRNA delivery system, demonstrating their ability to encapsulate siRNA, contain EV-surface markers, and functionally deliver siRNA to different cell types. These hybrids combine the benefits of both synthetic and biological drug delivery systems, showing altered functional behavior compared to liposomes and varying efficacy among recipient cell types.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Carme Fabrega, Anna Avino, Ramon Eritja
Summary: The article discusses the advancements in the therapeutic and diagnostic applications of nucleic acids over the past decade, including studies on siRNA modifications, novel conjugate designs, and the use of nanostructures for drug delivery. These interdisciplinary research efforts have expanded the applications of nucleic acids in various fields.
Review
Chemistry, Multidisciplinary
Agnieszka Tomaszewska-Antczak, Piotr Guga
Summary: This review summarizes the synthetic efforts on acyclic analogs of nucleic acids and evaluates their synthetic methods, thermal stability, and applications in biological and biochemical research as well as nanotechnology.
APPLIED SCIENCES-BASEL
(2021)
Review
Biotechnology & Applied Microbiology
Marwa A. Sallam, Supriya Prakash, Ninad Kumbhojkar, Charles Wyatt Shields, Samir Mitragotri
Summary: The advantages of dermal delivery of biomacromolecules include improved targetability, reduced systemic toxicity, and decreased degradation of drugs, while the main challenge lies in the barrier function of the skin. Current research is focused on improving the delivery of macromolecules to the skin using noninvasive methods, such as nucleic acids and antigens.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2021)
Article
Nanoscience & Nanotechnology
Guangqi Song, Haisi Dong, Danhui Ma, Heming Wang, Xinran Ren, Yishen Qu, Hao Wu, Jimin Zhu, Wu Song, Ying Meng, Li Wang, Taotao Liu, Xizhong Shen, Yicheng Zhao, Changfeng Zhu
Summary: Copper is essential for various life processes but can be highly toxic at excessive levels. In multiple malignancies, including pancreatic cancer, copper overload is common, and targeting metal ion transporters for treatment may offer an effective strategy. Therapeutic tFNAs may serve as vehicles for delivering small molecular RNAs to regulate copper intake in cancer cells, potentially attenuating cancer progression.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Multidisciplinary
Yang Gao, Xingyu Chen, Taoran Tian, Tao Zhang, Shaojingya Gao, Xiaolin Zhang, Yangxue Yao, Yunfeng Lin, Xiaoxiao Cai
Summary: Researchers have developed a dynamic lysosome-activated tetrahedral framework nucleic acid (tFNA) nanobox for encapsulating siRNA and achieving controlled release in cells, demonstrating excellent RNA protection and release effects.
ADVANCED MATERIALS
(2022)
Article
Pharmacology & Pharmacy
Walhan Alshaer, Hadil Zureigat, Arwa Al Karaki, Abdulfattah Al-Kadash, Lobna Gharaibeh, Ma'mon M. Hatmal, Alaa A. A. Aljabali, Abdalla Awidi
Summary: siRNA functions in gene silencing and targets disease-related genes, yet it faces issues such as low cellular uptake and susceptibility to degradation, requiring a carrier for protection and delivery.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lei Zhang, Xiulan Xie, Nemanja Djokovic, Katarina Nikolic, Dmitri Kosenkov, Frank Abendroth, Olalla Vazquez
Summary: This study demonstrates a reversible approach to regulate RNA splicing within primary patient-derived cells using synthetic photoswitches. The small molecule utilized enables conditional real-time control at mRNA and protein levels. Various experiments and assays confirmed light-dependent exon inclusion and an increase in the target functional protein. This work pioneers the potential of photopharmacology modulation in splicing and contributes to the advancement of RNA research.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Pharmacology & Pharmacy
Qixin Leng, Zuha Imtiyaz, Martin C. Woodle, A. James Mixson
Summary: In order to improve the accuracy of targeted therapy, a new approach has been developed to target and release therapy using the acidic pH of the tumor extracellular matrix and endosomes. By using pH-responsive nanoparticles to accumulate in the tumor and release the treatment in lower pH environments, greater specificity and targeting can be achieved. However, these pH-sensitive strategies are still in early stages of development with potential obstacles that may limit their clinical use.
Article
Biochemistry & Molecular Biology
Charnette Frederic, Gregory R. Wiedman
Summary: In this study, the possible interaction between azobenzene and aromatic amino acids was investigated, and evidence was found suggesting that primary protein structure could affect photoswitch activity. This research is of significance for further understanding the application of azobenzenes in biomolecules.
Article
Biochemistry & Molecular Biology
Matthew L. Hammill, Golam Islam, Jean-Paul Desaulniers
Article
Biochemistry & Molecular Biology
Andrew J. Varley, Matthew L. Hammill, Lidya Salim, Jean-Paul Desaulniers
NUCLEIC ACID THERAPEUTICS
(2020)
Article
Chemistry, Organic
Samira Barmaki, Arlene Ali, Jean-Paul Desaulniers, Yuri Bolshan
TETRAHEDRON LETTERS
(2020)
Article
Chemistry, Medicinal
Kouta Tsubaki, Matthew L. Hammill, Andrew J. Varley, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Biochemistry & Molecular Biology
Lidya Salim, Jean-Paul Desaulniers
Summary: RNA interference (RNAi) applications have advanced from experimental tools to approved therapeutics, but efficient delivery to target cells and tissues remains a major challenge.
NUCLEIC ACID THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Matthew L. Hammill, Lidya Salim, Kouta Tsubaki, Andrew J. Varley, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
Summary: The study demonstrates the synthesis of a cubane derivative phosphoramidite for incorporation into siRNAs, which showed excellent gene-silencing activity. Incorporating cubane modification in both sense and antisense strands led to viable duplexes with good biological activity, making it the first report of siRNAs bearing a cubane derivative.
Article
Chemistry, Organic
Ifrodet Giorgees, Fan Wu, Zhen Shen, Jean-Paul Desaulniers
Summary: Corrole-siRNAs offer a promising path for developing novel siRNA combination therapy. The conjugation of siRNAs with the photosensitizer, corrole, enables gene silencing and photodynamic therapy, creating a non-invasive dual therapy system. In vitro studies show that corrole-siRNA conjugates have promising results in gene silencing and PDT treatment, demonstrating their potential in future therapeutic applications.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Engineering, Environmental
Linda R. Lara-Jacobo, Golam Islam, Jean-Paul Desaulniers, Andrea E. Kirkwood, Denina B. D. Simmons
Summary: Wastewater-based epidemiology can detect the COVID-19 virus in wastewater. This study proposes a mass spectrometry-based method that can detect specific SARS-CoV-2 proteins several days earlier. The nonstructural protein pp1ab is found to be abundant in active COVID-19 cases.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Article
Chemistry, Medicinal
Matthew L. Hammill, Kouta Tsubaki, Lidya Salim, Andrew J. Varley, Ifrodet Giorgees, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
Summary: siRNAs have shown promise as gene-silencing therapeutics, but their cellular uptake remains a challenge. Researchers synthesized siRNAs with different hydrophobic phosphate triester linkages and evaluated their gene silencing effects without a transfection carrier. The best siRNAs exhibited effective gene silencing.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Matthew L. Hammill, Kouta Tsubaki, Yuwei Wang, Golam Islam, Mitsuru Kitamura, Tatsuo Okauchi, Jean-Paul Desaulniers
Summary: We report the synthesis of an ortho-functionalized tetrafluorinated azobenzene phosphoramidite for site-specific incorporation into RNA. The ortho-functionalized tetrafluorinated azobenzene is embedded in the antisense strand of an siRNA duplex to form a modified siRNA. In cell culture, the modified siRNA can be reversibly controlled through photoconversion.
Article
Chemistry, Organic
Charlene Fernandez, Ifrodet Giorgees, Eva Goss, Jean-Paul Desaulniers
Summary: RNA interference (RNAi) is a natural cellular process that silences target genes by degrading their mRNA. Developing an effective carrier-free delivery system for RNAi in the central nervous system (CNS) is a major challenge. Recently, lipid-conjugated systems using fatty acids have shown promise as safe and effective delivery systems for CNS cells. This study explores the use of sphingosine-modified siRNAs for carrier-free drug delivery to the CNS and finds promising results.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Lidya Salim, Jean-Paul Desaulniers
Summary: With the success of GalNAc and the need for extra-hepatic RNAi delivery systems, other receptor-targeting ligands, like folate, have gained attention. Despite the limitations of folate conjugation in RNAi, a cost-effective strategy to synthesize a novel folate derivative phosphoramidite for siRNA incorporation has been reported. These siRNAs were selectively taken up by folate receptor-expressing cancer cells and displayed potent gene-silencing activity.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Lidya Salim, Eva Goss, Jean-Paul Desaulniers
Summary: Chemical modifications in siRNAs, such as a novel glucose derivative reported in this study, can lead to potent gene-silencing activity and tolerance in both sense and antisense positions. Maintaining A-form helical formation and placing the modification at specific positions resulted in effective RNAi gene-silencing activity.
Review
Chemistry, Multidisciplinary
Andrew J. Varley, Jean-Paul Desaulniers
Summary: Therapeutic siRNAs have potent gene silencing abilities through the RNAi pathway, but off-target effects remain a challenge. Eliminating sense strand uptake can reduce off-target gene silencing and limit disruption to endogenous regulatory mechanisms, highlighting the importance of strand selection in future siRNA therapeutics.
Article
Chemistry, Organic
Matthew L. Hammill, Golam Islam, Jean-Paul Desaulniers
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)