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Tytuł:
Multidrug resistance-associated protein - reduction of expression in human leukaemia cells by antisense phosphorothioate olignucleotides.
Autorzy:
Niewiarowski, Wojciech
Gendaszewska, Edyta
Rębowski, Grzegorz
Wójcik, Marzena
>Mikołajczyk, Barbara
Soszyński, Mirosław
Bartosz, Grzegorz
Powiązania:
https://bibliotekanauki.pl/articles/1044273.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
antisense oligonucleotides
MRP
multidrug resistance
Opis:
Multidrug resistance-associated protein (MRP1) causes cellular drug resistance in several cancer cell lines. In this paper we show that antisense oligonucleotides decrease MRP1 expression in human leukaemia cells. We investigated biological activity of a series of 12 linear phosphorothioate oligonucleotides, complementary to several regions of MRP1 mRNA. The oligonucleotides were administered to leukaemia HL60/ADR cells overexpressing MRP1 protein. Then, the level of MRP1 mRNA was determined by means of semiquantitative RT-PCR and the protein level by reaction with specific monoclonal antibodies. Some of the investigated antisense oligonucleotides decrease the expression level of the MRP1 protein by 46% and its mRNA level by 76%.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1183-1188
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug resistance-associated protein 1: Their stability in fetal calf serum and human plasma.
Autorzy:
Rębowski, Grzegorz
Wójcik, Marzena
Boczkowska, Małgorzata
Gendaszewska, Edyta
Soszyński, Mirosław
Bartosz, Grzegorz
Niewiarowski, Wojciech
Powiązania:
https://bibliotekanauki.pl/articles/1044049.pdf
Data publikacji:
2001
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
human plasma
3' -exonuclease activity
multidrug resistance-associated protein
fetal calf serum
antisense hairpin loop oligonucleotides
Opis:
Multidrug resistance-associated protein (MRP1) is a transmembrane pump protein responsible for the efflux of chemotherapeutic drugs, an important cause of anticancer treatment failure. Trying to circumvent MRP-mediated resistance we designed and synthesized hairpin loops forming antisense oligodeoxyribonucleotides (ODNs), both phosphodiesters (PO-ODNs) and their phosphorothioate analogues (PS-ODNs), to reduce the protein expression by targeting its mRNA in a sequence specific manner. Melting temperature measurements as well as polyacrylamide gel electrophoresis supported the preferential formation of a secondary structure, which was expected to protect ODNs against 3'-exonuclease degradation. ODNs and PS-ODNs designed in this work were successfully tested as antisense inhibitors of the expression of MRP1 in the leukaemia HL60/ADR cell line. Foreseeing the necessity to perform clinical studies with such ODNs we investigated their stability against the 3'-exonuclease activity of fetal calf serum and human plasma. Under the conditions, corresponding to physiological ones, we observed high stability of hairpin loop forming ODNs, especially those containing longer (e.g. 7 base pair) stems. Comparative studies on the stability of chemically unmodified hairpin loop forming ODNs and their PS-counterparts indicated that endonuclease activity did not play any important role in the process of their nucleolytic degradation. Our studies provide strong evidence for high stability of chemically unmodified hairpin loop ODNs, making them an attractive alternative to phosphorothioate analogues commonly used in antisense strategy.
Źródło:
Acta Biochimica Polonica; 2001, 48, 4; 1061-1076
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Oligodeoxyadenylate stimulates the protein kinase activity of anti-DNA sIgA from human milk.
Autorzy:
Kit, Yuri
Kuligana, Elena
Semenov, Dimitry
Richter, Vladimir
Powiązania:
https://bibliotekanauki.pl/articles/1043844.pdf
Data publikacji:
2002
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
anti-DNA antibodies
abzymes
protein kinase activity
oligonucleotides
human milk
Opis:
Preparations of anti-DNA sIgA were obtained from human milk by sequential chromatography on protein A-sepharose, DEAE-fractogel and DNA-cellulose. The influence of oligonucleotides on protein kinase activity was investigated. It was discovered that incubation of anti-DNA sIgA with oligodeoxyriboadenylate d(A)12 stimulates the phosphorylation of polypeptides of sIgA in the presence of [γ-32P]ATP. The greatest was the incorporation of 32P into the sIgA H-chains. We also demonstrated stimulation of the casein kinase activity of anti-DNA sIgA by d(A)12. The stimulation of the protein kinase activity of anti-DNA sIgA by oligoriboadenylate r(A)12 was not detected.
Źródło:
Acta Biochimica Polonica; 2002, 49, 1; 291-294
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
RNA modulation, repair and remodeling by splice switching oligonucleotides.
Autorzy:
Kole, Ryszard
Williams, Tiffany
Cohen, Lisa
Powiązania:
https://bibliotekanauki.pl/articles/1043268.pdf
Data publikacji:
2004
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
RNA splicing; antisense oligonucleotides; genetic disease
Opis:
Targeting splicing by antisense oligonucleotides allows RNA modifications that are not possible with RNA interference or other antisense techniques that destine the RNA for destruction. By changing the ratio of naturally occurring splice variants the expression of mRNA is modulated. By preventing the use of an aberrant splice site created by a mutation and enforcing re-selection of correct splice sites the RNA is repaired. Antisense induced skipping of the exon that carries a nonsense mutation remodels the mRNA and restores the reading frame of the defective protein. All of the above approaches have clinical applications. Modulation of splice variants is particularly important since close to 60% of all genes code for alternatively spliced pre-mRNA.
Źródło:
Acta Biochimica Polonica; 2004, 51, 2; 373-378
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Tissue distribution of a menthyl-conjugated oligodeoxyribonucleotide antisense to PAI-1 mRNA
Autorzy:
Szemraj, Janusz
Al-Nedawi, Khalid
Chabielska, Ewa
Buczko, Wlodzimierz
Pawlowska, Zofia
Powiązania:
https://bibliotekanauki.pl/articles/1041329.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
PAI-1
antisense oligonucleotides
tissue distribution
Opis:
The inhibitory effect of numerous analogues of PO-16, an hexadecadeoxyribonucleotide antisense to sequences -22 to -17 of PAI-1 mRNA coding for a fragment of the signal peptide, on the expression of PAI-1 in endothelial cells, and physiological consequences of the subsequently reduced PAI-1 activity tested in vitro and in vivo, were described in our previous studies. Of particular interest was PO-16 5'-O-conjugated with menthyl phosphorothioate (MPO-16R). In this work, tissue localisation of MPO-16R labelled with [35S] phosphorothioate at the 3'-end, was determined. [35S]MPO-16R and control [35S]MPO-16R-SENSE oligonucleotides were administered intravenously into 22 rats and organ distribution of the labelled bioconjugates was assessed after 24 and 48 h. For this purpose, tissue sections were subjected to autoradiography, and quantitated by liquid scintillation after solubilisation. Overall clearance of radioactivity was already seen after 24 h, with the radioactivity recovered mainly in the kidney and liver. A smaller fraction of radioactivity was also retained in the spleen and heart. The kidney concentration of the labelled probe was higher than that of liver by 50%. The distribution of PAI-1 mRNA in untreated rat kidney, liver, spleen and heart established by two independent techniques: Ribonuclease Protection Assay and Real-Time PCR, shows the same pattern as that observed for [35S]MPO-16R antisense.
Źródło:
Acta Biochimica Polonica; 2005, 52, 4; 849-855
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Civilization diseases – therapeutic application of antisense strategy
Autorzy:
Bąkowska-Żywicka, Kamila
Tyczewska, Agata
Twardowski, Tomasz
Powiązania:
https://bibliotekanauki.pl/articles/703440.pdf
Data publikacji:
2008
Wydawca:
Polska Akademia Nauk. Czytelnia Czasopism PAN
Tematy:
civilization diseases
antisense oligonucleotides
novel therapies
Opis:
Modulation and regulation of biosynthesis process by means of antisense oligonucleotides lay the foundation for new therapeutic strategies, among others against cancer, viral or angiogenesis diseases. The aim of this account is the presentation of molecular basis of antisense strategy and mechanism of action of antisense oligonucleotides. Furthermore we present the state of art in clinical studies of application of antisense oligonucleotides in some of civilization diseases.
Źródło:
Nauka; 2008, 1
1231-8515
Pojawia się w:
Nauka
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Od syntezy oligonukleotydów do Mycoplasma laboratorium
Autorzy:
Laskowski, M.
Powiązania:
https://bibliotekanauki.pl/articles/273706.pdf
Data publikacji:
2011
Wydawca:
Roble
Tematy:
biologia syntetyczna
oligonukleotydy
Mycoplasma laboratorium
synthetic biology
oligonucleotides
Źródło:
LAB Laboratoria, Aparatura, Badania; 2011, 16, 3; 22-25
1427-5619
Pojawia się w:
LAB Laboratoria, Aparatura, Badania
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Zastosowania „click chemistry” w modyfikacjach nukleozydów i oligonukleotydów
Applications of click chemistry in modification of nucleosides and oligonucleotides
Autorzy:
Gładysz, M.
Milecki, J.
Powiązania:
https://bibliotekanauki.pl/articles/171589.pdf
Data publikacji:
2014
Wydawca:
Polskie Towarzystwo Chemiczne
Tematy:
click chemistry
CuAAC
modyfikacje nukleozydów
oligonukleotydy
DNA
kwas deoksyrybonukleinowy
RNA
kwas rybonukleinowy
Click Chemistry
nucleosides modifications
oligonucleotides
deoxyribonucleic acid
ribonucleic acid
Opis:
Since the year 2001 new ideology of clean and simple synthesis in organic chemistry has been established. The outstanding scientists Meldal and Sharpless presented their concepts of Click Chemistry. Among the reactions chosen for this concept the reaction of Copper(I) Catalyzed Alkyne-Azide Cycloaddition (CuAAC) became the most popular one. It is the basis of syntheses employed for building blocks synthesis in medicinal chemistry and material science. Libraries of potentially pharmacologically active anticancer and antivirus compounds possessing neutral triazol linkage could be easily obtained. Remarkable efficiency of CuAAC reaction influenced on DNA- and RNAbased synthesis of novel oligonucleotides derivatives. Many of nucleic acid molecular modifications found applications in enzymatic transformation, nucleic acid hybridization, molecular tagging and gene silencing. The CuAAC reaction allows for introducing modifications into practically every region of nucleoside/nucleotide/ oligonucleotide. This includes versatile modifications of the base moiety both aiming at the base pairing ability or specific labeling of the nucleoside unit. Different conjugates (bio-, fluorescent-, affinity- or spin labels) are being attached to the base part of the nucleic acid taking advantage of the presence of azide or alkyne substituents, which can be installed without great difficulty. Labeling at the sugar part of the nucleoside can be realized at the position 2’, 3’ or 5’, the latter two giving rise to the end-labeled oligonucleotides and the 2’ position serving as the attachment point for labeling inside the oligonucleotide chain. These kind of nucleic acid modifications are very promising. Versatility of CuAAC reactions is demonstrated by numerous examples of introducing modifications into practically every reactive site of the nucleotide/oligonucleotide molecule. The review systematically presents application of the “click” technique for modification of nitrogenous base, sugar or pseudosugar moiety or phosphorus center. Possibility of creating new kind of chain linkage, devoid of negative charge and nuclease resistant is also shown. This allows to design a new class of nucleic acid analogues, similar in its DNA-mimicking properties to PNA’s.
Źródło:
Wiadomości Chemiczne; 2014, 68, 7-8; 617-643
0043-5104
2300-0295
Pojawia się w:
Wiadomości Chemiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Synteza modyfikowanych oligonukleotydów zawierających stereozdefiniowane internukleotydowe wiązania tiofosforanowe
Synthesis of modified oligonucleotides containing stereodefined internucleotide phosphorothioate bonds
Autorzy:
Radzikowska, E.
Kaczmarek, R.
Baraniak, J.
Powiązania:
https://bibliotekanauki.pl/articles/172219.pdf
Data publikacji:
2015
Wydawca:
Polskie Towarzystwo Chemiczne
Tematy:
oligonukleozydotiofosforany
oligonukleotydy antysensowe
synteza modyfikowanych oligonukleotydów
synteza stereospecyficzna
oligo(deoxy)ribonucleoside phosphorothioates
antisense oligonucleotides
synthesis of modified oligonucleotide
stereospecific synthesis
Opis:
Synthetic oligonucleotides constitute an important class of compounds which can exhibit biological activity. As potential drugs they could be employed in antisense strategy by acting on the pathogenic mRNA, causing inactivation of the target molecules during the translation process [1]. Ideal antisense agent (ASO) should be resistant to exo and/or endonucleases, exhibit a suitable pharmacological and pharmacokinetic profile and exhibits high binding affinity towards the target mRNA. To improve some properties of the ASO plethora of the chemical modifications introduced within the nucleobase, sugar unit and internucleotide linkage are investigated [3]. Among them, phosphorothioate oligonucleotides (PS-oligo), created by replacing one of the nonbridging oxygen atoms with a sulfur atom, are the major representatives of DNA analogs. PS-oligo display several attractive features like nuclease resistance, activation of RNase H, and good pharmacokinetic properties [1]. Replacement of one of two nonbridging oxygens at phosphorus by sulfur induces asymmetry at the phosphorus atom. Hence, the synthesized oligo(nucleoside phosphorothioate) is a mixture of 2n diastereomers (where n is the number of internucleotide phosphorothioate functions). Therefore the actual biological activity of the P-chiral oligonucleotide analogues, (e.g., interactions with proteins or nucleic acids) may depend on stereochemical factors [7]. One has to keep in mind that the phosphoramidite [5] and H-phosphonate [32] methodologies (commonly used to prepare PS-oligo) are nonstereospecific and give a mixture of 2n diastereomers. Thus, various methods have been elaborated to synthesize these P-chiral oligonucleotide analogs in a stereocontrolled manner [15, 17], among them the oxathiaphospholane method developed by Stec et al. [18], the method utilizing nucleoside 3’-O-(3-N-acyl)oxazaphospholidine derivatives as monomer units [19], and the method based on a stereoselective synthesis of nucleoside 3’-O-oxazaphospholidine monomers [21, 22] are the most significant.
Źródło:
Wiadomości Chemiczne; 2015, 69, 11-12; 957-981
0043-5104
2300-0295
Pojawia się w:
Wiadomości Chemiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Chromatograficzna analiza związków budujących kwasy nukleinowe
Chromatographic analysis of nucleic acids constituents
Autorzy:
Studzińska, S.
Rola, R.
Łobodziński, F.
Krzemińska, K.
Powiązania:
https://bibliotekanauki.pl/articles/172180.pdf
Data publikacji:
2016
Wydawca:
Polskie Towarzystwo Chemiczne
Tematy:
nukleozydy
nukleotydy
oligonukleotydy
chromatografia cieczowa
czułość
selektywność
nucleosides
nucleotides
oligonucleotides
liquid chromatography
sensitivity
selectivity
Opis:
Understanding the characteristics, role and structure of nucleic acids allowed to answer questions about the disease processes. Today, nucleic acids and their constituents are tools, which are used by molecular biology in medicine and biotechnology. Antisense and gene therapy are intensively developing methods for possible treating or preventing disease. They use short fragments of DNA or RNA - oligonucleotides to silence the genes expression. They are not the only ones that allow analytical chemists to obtain information about the state of our body. Determination of modified nucleoside allows detection of cancer, while analysis of nucleotides allows the estimation of strengthening the immune system. There is a great need of sensitive, selective and precise methods of separation of nucleosides, nucleotides and oligonucleotides and their qualitative and quantitative analysis. Consequently liquid chromatography (LC) is the most commonly used for analysis of nucleic acid constituents. The most widely used modes of LC include Ion Exchange Chromatography (IEC) and Reversed Phase High Performance Liquid Chromatography (RP HPLC). Both techniques have their advantages and disadvantages in the analysis of nucleosides, nucleotides and oligonucleotides. In the case of IEC it is necessary to use high concentrations of the salt in the mobile phase or concentration gradients, which considerably limits the possibility of using MS detection. RP HPLC can be coupled with MS detection but only when volatile salts are mobile phase components. On the other hand there is a significant problem is the lack of sufficient selectivity for the most polar nucleosides and nucleotides. RP HPLC MS is still most often used in the determination of nucleosides and nucleotides, due to its high sensitivity and a comprehensive qualitative analysis. Another system used for the HPLC analysis of oligonucleotides is Ion Pair Reversed Phase High Performance Liquid Chromatography (IP RP HPLC). These compounds can not be analyzed by RP HPLC due to their high polarity. The advantage of IP RP HPLC is selectivity, achieved by a suitable choice of mobile phase composition and the possibility of using MS. A disadvantage of IP RP HPLC in the analysis of oligonucleotides is however lower sensitivity compared to RP HPLC. During the last few years Hydrophilic Interaction Liquid Chromatography (HILIC) was applied for the separation of mixtures of nucleosides, nucleotides, oligonucleotides extracted from a biological or food samples. The presented results demonstrate the usefulness of this method, however, the resolving power is limited due to the asymmetric peak shape. On the other hand proper selection of the mobile and stationary phase can lead to a high selectivity in the analysis of the most polar nucleosides, nucleotides and oligonucleotides, which can not be separated by RP HPLC.
Źródło:
Wiadomości Chemiczne; 2016, 70, 9-10; 633-656
0043-5104
2300-0295
Pojawia się w:
Wiadomości Chemiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Topical treatment of LdMNPV-infected gypsy moth caterpillars with 18 nucleotides long antisense fragment from LdMNPV IAP3 gene triggers higher levels of apoptosis in infected cells and mortality of the pest
Autorzy:
Oberemok, Volodymyr V.
Laikova, Kateryna V.
Zaitsev, Alexey S.
Nyadar, Palmah M.
Gninenko, Yuri I.
Gushchin, Vladimir A.
Makarov, Valentin V.
Agranovsky, Alexey A.
Powiązania:
https://bibliotekanauki.pl/articles/961638.pdf
Data publikacji:
2017
Wydawca:
Polska Akademia Nauk. Czytelnia Czasopism PAN
Tematy:
baculoviral infection
dna insecticides
dna oligonucleotides
forest and
crop protection
gypsy moth
iap genes
Opis:
The high efficiency of baculovirus infection is partially explained by the ability of the virus to suppress host defense machinery connected with the apoptosis pathway. Members of the baculovirus gene family, inhibitors of apoptosis (vIAPs), have been shown to inhibit apoptosis in baculovirus-infected cells. Here we showed that treatment of the LdMNPV- -infected 1st instar gypsy moth (Lymantria dispar) caterpillars with sense (oligoBIR) and antisense (oligoRING) DNA oligonucleotides from the LdMNPV IAP3 gene induced elevated mortality of the insects. Apoptotic DNA ladder assay showed that the leading role in this phenomenon is played by the antisense oligoRING fragment of the vIAP3 gene. These results imply that the application of both antisense DNA oligonucleotides from vIAP genes and baculovirus preparations (one following the other) may be a potential method for plant protection against insect pests.
Źródło:
Journal of Plant Protection Research; 2017, 57, 1
1427-4345
Pojawia się w:
Journal of Plant Protection Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Molekularne podłoże i terapia rdzeniowego zaniku mięśni
Molecular basis and therapy of spinal muscular atrophy
Autorzy:
Szczerba, Anna
Śliwa, Aleksandra
Żarowski, Marcin
Jankowska, Anna
Powiązania:
https://bibliotekanauki.pl/articles/2045802.pdf
Data publikacji:
2018
Wydawca:
Polskie Towarzystwo Neurologów Dziecięcych
Tematy:
rdzeniowy zanik mięśni
gen SMN
białko SMN
antysensowe oligonukleotydy
nusinersen
terapia genowa
AVXS
spinal muscular atrophy
SMN gene
SMN protein
antisense oligonucleotides Spinraza
gene therapy
Zolgensma
Opis:
Rdzeniowy zanik mięśni, SMA (spinal muscular atrophy) to genetyczna choroba powodowana mutacją genu SMN1 i w konsekwencji niedoborem białka SMN (survival of motor neuron), które odgrywa kluczową rolę w regulacji ekspresji genów w motoneuronach. Jego brak prowadzi do zwyrodnienia i apoptozy komórek rogów przednich rdzenia kręgowego i w konsekwencji zaniku mięśni. Gen SMN w ludzkim genomie występuje w co najmniej dwóch kopiach: SMN1 i SMN2. Oba geny kodują identyczne białko, jednak transkrypty SMN1 mają pełną długość (FL-SMN), a 90% transkryptów SMN2 jest pozbawiona eksonu 7 (SMN-Δ7), co powoduje niefunkcjonalność białka. FL-SMN jest niezbędne do prawidłowego przeprowadzenia procesu splicingu. Niskie stężenie białka SMN upośledza także dynamikę szkieletu aktynowego, co skutkuje zahamowaniem wzrostu aksonów motoneuronów. Dotychczasowe leczenie SMA opierało się głównie na działaniach neuroprotekcyjnych i wzmacniających siłę mięśni. Obecnie, dzięki wykorzystaniu antysensowych nukleotydów (ASO), możliwa jest terapia modulująca przebieg splicingu, która pozwala na włączenie eksonu 7 do transkryptu SMN2. Takim ASO jest nusinersen, który został zatwierdzony do użytku w USA i Europie; jest on w pełni refundowany w Polsce. Terapeutyk jest przeznaczony do leczenia pacjentów ze wszystkimi typami SMA w każdym wieku. Inną strategią leczenia jest terapia genowa pod nazwą onasemnogene abeparvovec (AVXS-101), polegająca na wprowadzeniu do organizmu pacjenta prawidłowej kopii genu SMN1. Nośnikiem genu terapeutycznego, wnikającego jedynie do komórek układu nerwowego, jest wektor wirusowy AAV. Lek ten został zatwierdzony przez FDA w leczeniu SMA pacjentów poniżej 2. roku życia.
Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the SMN1 gene and, consequently, a deficiency of the SMN (survival of motor neuron) protein, which plays a key role in regulating gene expression in motoneurons. Its absence leads to degeneration and apoptosis of the anterior horn cells of the spinal cord and, as a consequence, to muscular atrophy. In the human genome the SMN gene is found in at least two copies: SMN1 and SMN2. Both genes encode the same protein, however, SMN1 transcripts are full-length (FL-SMN) and 90% of SMN2 transcripts are deprived of exon 7 (SMN-Δ7), which causes the protein to be non-functional. FL-SMN is necessary for proper splicing process. Low concentration of the SMN protein also impairs the dynamics of the actin skeleton, which results in inhibition of motoneuron axon growth. Hitherto SMA treatment was based mainly on neuroprotective and muscle strength enhancing approaches. Currently, thanks to the use of antisense nucleotides (ASO), it is possible to modulate the splicing process of SMN2, which allows the incorporation of exon 7 into the SMN2 transcripts. Nusinersen is an ASO that has been approved for clinical use in USA and Europe; it is fully refunded in Poland. The therapy is intended for the treatment of patients with all types of SMA at all ages. Another treatment strategy is the gene therapy called onasemnogene abeparvovec (AVXS-101) which allows introducing the correct copy of the SMN1 gene into the patient’s body. The carrier of the therapeutic gene that enters only the cells of the nervous system is an AAV viral vector. This drug has been approved by the FDA for the treatment of SMA in patients under 2 years of age.
Źródło:
Neurologia Dziecięca; 2018, 27, 55; 39-46
1230-3690
2451-1897
Pojawia się w:
Neurologia Dziecięca
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Insecticidal activity of three 10–12 nucleotides long antisense sequences from 5.8S ribosomal RNA gene of gypsy moth Lymantria dispar L. against its larvae
Autorzy:
Oberemok, V.V.
Laikova, K.V.
Useinov, R.Z.
Gal`chinsky, N.V.
Novikov, I.A.
Yurchenko, K.A.
Volkov, M.E.
Gorlov, M.V.
Brailko, V.A.
Plugatar
Powiązania:
https://bibliotekanauki.pl/articles/2084849.pdf
Data publikacji:
2019
Wydawca:
Polska Akademia Nauk. Czytelnia Czasopism PAN
Tematy:
antisense oligonucleotides
DNA insecticides
gypsy moth
insect pest control
Lymantria dispar
5.8S ribosomal RNA
Opis:
5.8S ribosomal RNA plays an important role in protein synthesis and eukaryotic ribosome translocation. Contact DNA insecticides based on antisense fragments of 5.8S ribosomal RNA gene of gypsy moth Lymantria dispar L. showed prospective insecticidal activity on its larvae. The most pronounced insecticidal effect was found for antisense fragments 10 and 11 nucleotides long (oligoRIBO-10 and oligoRIBO-11), whereas 12 nucleotides long fragment (oligoRIBO-12) caused the lowest level of insect mortality. This data corresponds to results obtained earlier using rabbit reticulocyte and wheat germ extracts, where maximum inhibition of protein synthesis was observed when a relevant oligomer 10-11 nucleotides long was used, whilst longer chain lengths resulted in reduced inhibition. Using oligoRIBO-11 fragment we have shown penetration of antisense oligonucleotides to insect cells through insects’ exoskeletons. MALDI technique registered the penetration of the oligoRIBO-11 fragment into insect cells after 30 min and a significant response of insect cells to the applied oligonucleotide after 60 min, which indicates not only that the oligonucleotide enters the insect cells, but also the synthesis of new substances in response to the applied DNA fragment. Contact DNA insecticides developed from the L. dispar 5.8S ribosomal RNA gene provide a novel biotechnology for plant protection using unmodified antisense oligonucleotides.
Źródło:
Journal of Plant Protection Research; 2019, 59, 4; 561-564
1427-4345
Pojawia się w:
Journal of Plant Protection Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Proces składania RNA jako cel oddziaływania terapeutycznego
Therapeutic targeting of alternative splicing
Autorzy:
Paluszczak, Jarosław
Powiązania:
https://bibliotekanauki.pl/articles/762699.pdf
Data publikacji:
2019-12-29
Wydawca:
Polskie Towarzystwo Farmaceutyczne
Tematy:
alternatywne składanie RNA
antysensowne oligonukleotydy
nusinersen
eteplirsen
modulatory składania RNA
alternative splicing
antisense oligonucleotides
RNA splicing modulators
Opis:
Gene transcription leads to the generation of pre-mRNA molecules which contain both coding sequences (exons) and intervening non-coding sequences (introns). The primary transcript needs further processing which involves the excision of introns and ligation of exons. This process is called RNA splicing. Nearly all primary transcripts undergo alternative forms of splicing, which may lead to exon skipping or intron inclusion in the final mRNA. Thus, the translation of alternatively spliced RNA molecules results in the formation of slightly different proteins, which may, in some cases, exert antagonistic activity. Splicing is a multistage process which is conducted by a complex machinery comprising small nuclear RNA molecules and many proteins called splicing factors. The process undergoes precise regulation by means of cis acting internal RNA sequences and trans acting protein factors which may either enhance or silence the splicing of an exon. Many diseases are associated with aberrations of alternative splicing and its modulation may be used therapeutically, e.g. for the treatment of spinal muscular atrophy (SMA) or Duchenne muscular dystrophy (DMD). This article presents current knowledge of the ways of pharmacological modulation of alternative splicing. The focus is on the use of those therapeutics which have been already approved for clinical application or have entered clinical trials. The chemistry and mechanism of action of specific splice switching oligonucleotides is presented. Nusinersen promotes exon inclusion during splicing of SMN2 and is used for SMA treatment. On the other hand, eteplirsen is an oligonucleotide promoting exon skipping during splicing of mutated DMD and has been conditionally approved for DMD treatment. Moreover, small molecule modulators of alternative splicing (e.g. branaplam) are also described. The dynamic developments in this field should result in the approval of new drugs acting by the modulation of alternative splicing in the nearest future.
Powstająca w wyniku transkrypcji genu cząsteczka pre-mRNA zawiera odcinki kodujące (eksony) poprzedzielane odcinkami niekodującymi (intronami). Pierwotny transkrypt wymaga obróbki, która polega między innymi na wycinaniu intronów i łączeniu eksonów. Proces ten nazywany jest składaniem RNA. W przypadku niemal wszystkich transkryptów, składanie pre-mRNA przebiega w komórkach alternatywnymi drogami, na przykład prowadząc do wykluczenia jednego z eksonów z ostatecznego transkryptu, lub włączenia jednego z intronów. Proces składania RNA przeprowadzany jest przez skomplikowaną maszynerię złożoną z małych cząsteczek RNA i białek, i podlega precyzyjnej regulacji. Wiele chorób związanych jest z nieprawidłowościami alternatywnego składania RNA, a modulacja tego procesu może być wykorzystana terapeutycznie, między innymi w leczeniu rdzeniowego zaniku mięśni (SMA, ang. spinal muscular atrophy) czy dystrofii mięśniowej Duchenne’a (DMD). Celem artykułu jest przedstawienie wiedzy na temat farmakologicznych możliwości wpływania na proces składania RNA. Nacisk położono na scharakteryzowanie tych terapeutyków, które zostały już zarejestrowane do użytku klinicznego, lub które są w trakcie zaawansowanych badań klinicznych. Zaprezentowano budowę chemiczną i mechanizm działania oligonukleotydowych przełączników składania RNA. Nusinersen stymuluje włączanie eksonu 7 w trakcie składania SMN2 i jest wykorzystywany w leczeniu SMA. Eteplirsen, który stymuluje pomijanie eksonu 51 w trakcie składania zmutowanych wariantów DMD, został warunkowo dopuszczony do leczenia DMD w USA. Opisano także drobnocząsteczkowe modulatory alternatywnego składnia RNA, np. branaplam. Dynamiczny rozwój tego obszaru badań stwarza szansę na wprowadzone w najbliższej przyszłości do lecznictwa kolejnych leków, których mechanizm działania oparty będzie na modulacji alternatywnego składania RNA.
Źródło:
Farmacja Polska; 2019, 75, 11; 605-616
0014-8261
2544-8552
Pojawia się w:
Farmacja Polska
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
A breakthrough in the efficiency of contact DNA insecticides: rapid high mortality rates in the sap-sucking insects Dynaspidiotus britannicus Comstock and Unaspis euonymi Newstead
Autorzy:
Gal`chinsky, N.
Useinov, R.
Yatskova, E.
Laikova, K.
Novikov, I.
Gorlov, M.
Trikoz, N.
Sharmagiy, A.
Plugatar, Y.
Oberemok, V.
Powiązania:
https://bibliotekanauki.pl/articles/2082776.pdf
Data publikacji:
2020
Wydawca:
Polska Akademia Nauk. Czytelnia Czasopism PAN
Tematy:
antisense oligonucleotides
DNA insecticides
insect pest control
sap-sucking
insects
28S ribosomal RNA
Opis:
In this short communication describing experiments carried out on the larvae of two insects, Unaspis euonymi Comstock (feeding on Euonymus japonicus Thunb.) and Dynaspidiotus britannicus Newstead (feeding on Laurus nobilis L.), we evaluate for the first time the efficiency of using DNA insecticides in the control of sap-sucking insects, including armored scale insects. Over a period of 10 days, high insect mortality was detected in both U. euonymi and D. britannicus, accompanied by a significant decrease in the concentration of target RNAs. At the same time, no visible changes were observed when the leaves of the host plants were subjected to treatment with DNA insecticides for one month. The results show the high efficiency of DNA insecticides used against hemipteran insect pests. It is noteworthy that the high efficiency of DNA insecticides and their low cost in comparison with RNA preparations provides a safe and extremely promising potential vehicle for the control of sap-sucking insects.
Źródło:
Journal of Plant Protection Research; 2020, 60, 2; 220-223
1427-4345
Pojawia się w:
Journal of Plant Protection Research
Dostawca treści:
Biblioteka Nauki
Artykuł
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