Abstract:
:RNA interference represents a potent intervention for cancer treatment but requires a robust delivery agent for transporting gene-modulating molecules, such as small interfering RNAs (siRNAs). Although numerous molecular approaches for siRNA delivery are adequate in vitro, delivery to therapeutic targets in vivo is limited by payload integrity, cell targeting, efficient cell uptake, and membrane penetration. We constructed nonviral biomaterials to transport small nucleic acids to cell targets, including tumor cells, on the basis of the self-assembling and cell-penetrating activities of the adenovirus capsid penton base. Our recombinant penton base chimera contains polypeptide domains designed for noncovalent assembly with anionic molecules and tumor homing. Here, structural modeling, molecular dynamics simulations, and functional assays suggest that it forms pentameric units resembling viral capsomeres that assemble into larger capsid-like structures when combined with siRNA cargo. Pentamerization forms a barrel lined with charged residues mediating pH-responsive dissociation and exposing masked domains, providing insight on the endosomolytic mechanism. The therapeutic impact was examined on tumors expressing high levels of HER3/ErbB3 that are resistant to clinical inhibitors. Our findings suggest that our construct may utilize ligand mimicry to avoid host attack and target the siRNA to HER3+ tumors by forming multivalent capsid-like structures.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Alonso-Valenteen F,Pacheco S,Srinivas D,Rentsendorj A,Chu D,Lubow J,Sims J,Miao T,Mikhael S,Hwang JY,Abrol R,Medina Kauwe LKdoi
10.1093/nar/gkz900subject
Has Abstractpub_date
2019-12-02 00:00:00pages
11020-11043issue
21eissn
0305-1048issn
1362-4962pii
5588347journal_volume
47pub_type
杂志文章abstract::Helicase-nuclease systems dedicated to DNA end resection in preparation for homologous recombination (HR) are present in all kingdoms of life. In thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we show that HerA...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1157
更新日期:2012-04-01 00:00:00
abstract::H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address thes...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks773
更新日期:2012-10-01 00:00:00
abstract::The response to amino acid (AA) limitation of the entire aminoacyl-tRNA synthetase (ARS) gene family revealed that 16/20 of the genes encoding cytoplasmic-localized enzymes are transcriptionally induced by activating transcription factor 4 (Atf4) via C/ebp-Atf-Response-Element (CARE) enhancers. In contrast, only 4/19 ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw667
更新日期:2016-11-16 00:00:00
abstract::Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky162
更新日期:2018-05-18 00:00:00
abstract::This review takes a second look at a set of mRNAs that purportedly employ an alternative mechanism of initiation when cap-dependent translation is reduced during mitosis or stress conditions. A closer look is necessary because evidence cited in support of the internal initiation hypothesis is often flawed. When putati...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gki958
更新日期:2005-11-28 00:00:00
abstract::Previous work has demonstrated that the yeast SPT3 gene is required for transcription from delta sequences, the long terminal repeats that flank yeast Ty elements. In spt3 null mutants, transcription fails to initiate in delta sequences and instead initiates farther downstream. Null mutations in SPT3 cause other mutan...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.17.6885
更新日期:1986-09-11 00:00:00
abstract::The 2'-5' oligoadenylate synthetases form a well conserved family of interferon induced proteins, presumably present throughout the mammalian class. Using the Expressed Sequence Tag databases, we have identified a novel member of this family. This protein, which we named p59 2'-5' oligoadenylate synthetase-like protei...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.18.4121
更新日期:1998-09-15 00:00:00
abstract::The 5'-flanking region of the bovine prolactin gene was cloned and sequenced. The expression of chimeric gene constructs containing 5'-flanking DNA fragments from the prolactin gene joined to a reporter gene encoding human growth hormone (hGH) was examined using transiently transfected rat pituitary cells. Prolactin n...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
更新日期:1990-08-25 00:00:00
abstract::The persistence of fetal hemoglobin in many patients with deletion type beta thalassemias and the expression patterns of human globin genes in transgenic mice suggest that gamma- to beta-globin gene switching results primarily from competition of gamma- and beta-globin genes for interaction with the beta-globin locus ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.14.2736
更新日期:2000-07-15 00:00:00
abstract::Adenosine-to-inosine (A-to-I) RNA editing is a common post transcriptional modification. It has a critical role in protecting against false activation of innate immunity by endogenous double stranded RNAs and has been associated with various regulatory processes and diseases such as autoimmune and cardiovascular disea...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa305
更新日期:2020-06-19 00:00:00
abstract::The primary structure of the E. coli rpoC gene (5321 base pairs) coding the beta'-subunit of RNA polymerase as well as its adjacent segment have been determined. The structure analysis of the peptides obtained by cleavage of the protein with cyanogen bromide and trypsin has confirmed the amino acid sequence of the bet...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.13.4035
更新日期:1982-07-10 00:00:00
abstract::Explicit solvent molecular dynamics (MD) was used to describe the intrinsic flexibility of the helix 42-44 portion of the 23S rRNA (abbreviated as Kt-42+rGAC; kink-turn 42 and GTPase-associated center rRNA). The bottom part of this molecule consists of alternating rigid and flexible segments. The first flexible segmen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm245
更新日期:2007-01-01 00:00:00
abstract::Substantial amounts of DNA (at least 25 microgram per cm2) can be stably bound to diazobenzyloxymethyl (DBM)-paper. Complementary RNA will hybridize to the DNA paper almost completely in 24 hours. Using several different conditions of hybridization and washing, the background of RNA bound non-specifically is very low ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.1.195
更新日期:1979-01-01 00:00:00
abstract::A number of different protecting groups were compared with respect to their usefulness for protection of 2'-hydroxyl functions during synthesis of oligoribonucleotides using the H-phosphonate approach. The comparison was between the t-butyldimethylsilyl (t-BDMSi), the o-chlorobenzoyl (o-CIBz), the tetrahydropyranyl (T...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.1.94
更新日期:1994-01-11 00:00:00
abstract::DNA breaks occur during many processes in mammalian cells, including recombination, repair, mutagenesis and apoptosis. Here we report a simple and rapid method for assaying DNA breaks and identifying DNA breaksites. Breaksites are first tagged and amplified by ligation-mediated PCR (LM-PCR), using nested PCR primers t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.6.e33
更新日期:2001-03-15 00:00:00
abstract::The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and re...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1095
更新日期:2018-01-04 00:00:00
abstract::Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets ...
journal_title:Nucleic acids research
pub_type: 杂志文章,meta分析
doi:10.1093/nar/gkp093
更新日期:2009-05-01 00:00:00
abstract::Differential display of mRNA is a simple, sensitive and powerful method to identify differentially expressed gene fragments. The main drawback of differential display is the lack of reproducibility and the inability to read and compare complex gels. This issue results from employing unoptimized primer combinations and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.3.854
更新日期:1998-02-01 00:00:00
abstract::A dinucleoside monophosphate, 6,2'-anhydro-6-oxy-1-beta-D-arabinofuranosyluracil-phosphoryl- (3'-5')-6,2'-anhydro-6-oxy-1-beta-D-arabinofuranosyluracil (I) was synthesized by the condensation reaction using DCC from 5'-monomethoxytrityl derivative(VII) and 3'-acetyl-5'-phosphate(X) of the monomer units. Yield was ca. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/1.3.479
更新日期:1974-03-01 00:00:00
abstract::SUPERFAMILY provides structural, functional and evolutionary information for proteins from all completely sequenced genomes, and large sequence collections such as UniProt. Protein domain assignments for over 900 genomes are included in the database, which can be accessed at http://supfam.org/. Hidden Markov models ba...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn762
更新日期:2009-01-01 00:00:00
abstract::Mitome is a specialized mitochondrial genome database designed for easy comparative analysis of various features of metazoan mitochondrial genomes such as base frequency, A+T skew, codon usage and gene arrangement pattern. A particular function of the database is the automatic reconstruction of phylogenetic relationsh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm763
更新日期:2008-01-01 00:00:00
abstract::DNA2 nuclease/helicase is a structure-specific nuclease, 5'-to-3' helicase, and DNA-dependent ATPase. It is involved in multiple DNA metabolic pathways, including Okazaki fragment maturation, replication of 'difficult-to-replicate' DNA regions, end resection, stalled replication fork processing, and mitochondrial geno...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkz1101
更新日期:2020-01-10 00:00:00
abstract::Organisms growing at elevated temperatures face the challenge of maintaining the integrity of their genetic materials. Archaea possess unique chromatin proteins for gene organization and information processing. We present the solution structure of Sso7c4 from Sulfolobus solfataricus, which has a homodimeric DNA-bindin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr283
更新日期:2011-08-01 00:00:00
abstract::Elongation factor P (EF-P) is a conserved ribosome-binding protein that structurally mimics tRNA to enable the synthesis of peptides containing motifs that otherwise would induce translational stalling, including polyproline. In many bacteria, EF-P function requires post-translational modification with (R)-β-lysine by...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1296
更新日期:2014-03-01 00:00:00
abstract::Extracts of the human glioma cell line A1235 (lacking O(6)-methylguanine-DNA methyltransferase) are known to restore a G:T mismatch to a normal G:C pair in a G:T-containing model (45 bp) DNA substrate. Herein we demonstrate that substitution of G:T with O(6)-methylguanine:T (m6G:T) results in extract-induced intra-str...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.11.2409
更新日期:2001-06-01 00:00:00
abstract::The synthesis of stable RNA in Mycoplasma capricolum was studied by [32P] labeling of cellular RNA of cells grown in a partially-defined medium in the presence or absence of an amino acid mixture supplement. The results indicate that M. capricolum employs the same stringent control mechanism used by E. coli cells, as ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.15.3641
更新日期:1981-08-11 00:00:00
abstract::Plasmid DNA incubated in interphase Xenopus egg extracts is normally assembled into chromatin and then into synthetic nuclei which undergo one round of regulated replication. During a study of restriction endonuclease cut plasmid replication intermediates (RIs) by the Brewer-Fangman 2D gel electrophoresis technique, w...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.10.2187
更新日期:2000-05-15 00:00:00
abstract::DNA polymerase III (DNA pol III) efficiently replicates the Escherichia coli genome, but it cannot bypass DNA damage. Instead, translesion synthesis (TLS) DNA polymerases are employed to replicate past damaged DNA; however, the exchange of replicative for TLS polymerases is not understood. The umuD gene products, whic...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks229
更新日期:2012-07-01 00:00:00
abstract::Single-stranded DNA-binding proteins (SSBs) support DNA replication by protecting single-stranded DNA from nucleolytic attack, preventing intra-strand pairing events and playing many other regulatory roles within the replisome. Recent developments in single-molecule approaches have led to a revised picture of the repl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz090
更新日期:2019-05-07 00:00:00
abstract::Cationic aromatic tricyclic compounds including triphenylmethane dyes, phenazines, phenoxazines, acridines, phenothiazines, phenanthridinium compounds, anthracenes and xanthene dyes, which amplify cell killing in phleomycin-treated Escherichia coli B cells also modified phleomycin-induced breakdown of DNA to acid-solu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.23.9083
更新日期:1984-12-11 00:00:00