Strand Nucleotide Research Articles

HIV-1 Reverse Transcriptase Pausing at Bulky 2' Adducts is Relieved by Deletion of the RNase H Domain

Pausing by reverse transcriptase (RT) during retroviral replication increases the frequency of homologous strand transfer, nucleotide misincorporation, and non-templated nucleotide addition. Pausing frequency increases at sites of DNA damage or upon incorporation of nucleotide analogs with steric barriers. These lesions thus likely stimulate mutations leading to resistant viral strains that escape drug treatments or immune surveillance. To study the response of retroviral RTs to bulky 2' adducts, a ribozyme-catalyzed reaction was used to generate an RNA template strand containing a thiophosphate adduct at a specific 2'-hydroxyl located upstream from a polyadenosine sequence. Subsequent alkylation increased the size of the adduct. Polymerization readthrough efficiencies were compared for mature RTs derived from HIV-1 (p66/p51), AMV (p95/p63), MMLV (p80 monomer), and a truncated version of HIV-1 RT lacking the RNase H domain (p51/p51 homodimer). Readthrough at the 2' lesion was markedly greater for the p51/p51 homodimer of HIV-1 RT than for the other enzymes, suggesting that the presence of the RNase H domain increases the probability that the modified primer/template will encounter a barrier to translocation. Comparison to published structures suggests potential unfavorable interactions between the 2' adduct and W24, F61, I63, D76, and R78 in the fingers domain of the RT. We propose that the enhanced readthrough observed upon RNase H domain deletion alters the trajectory of the primer/template in this region that diminishes steric and electrostatic clash with these residues. The template also included a penta-adenosine sequence that induced pausing in the order MMLV > HIV-1 (p66/p51) > AMV ≈ HIV-1 (p51/p51).

Thermodynamics of competitive surface adsorption on DNA microarrays

Gene microarrays provide a powerful functional genomics technology which permits theexpression profiling of tens of thousands of genes in parallel. The basic idea of theirfunctioning is based on the sequence specificity of probe–target interactions combined withfluorescence detection. In reality, this straightforward principle is opposed by thecomplexity of the experimental system due to imperfections of chip fabrication and RNApreparation, due to the non-linearity of the probe response and especially due tocompetitive interactions which are inherently connected with the high throughputcharacter of the method. We theoretically analysed aspects of the hybridization of DNAoligonucleotide probes with a complex multicomponent mixture of RNA fragments,such as the effect of different interactions between nucleotide strands competingwith the formation of specific duplexes, electrostatic and entropic blocking, thefragmentation of the RNA, the incomplete synthesis of the probes and ‘zipping’ effects inthe oligonucleotide duplexes. The effective hybridization affinities of microarrayprobes are considerably smaller than those for bulk hybridization owing to theeffects discussed, but they correlate well with the bulk data on a relative scale. Ingeneral, the hybridization isotherms of microarray probes are shown to deviatefrom a Langmuir-type behaviour. Nevertheless isotherms of the Langmuir or Sipstype are predicted to provide a relatively simple description of the non-linear,probe-specific concentration dependence of the signal intensity of microarrayprobes.

DNA-Programmed Control of Photosensitized Singlet Oxygen Production

DNA sequence-controlled on-and-off switching of a singlet oxygen sensitizer has been developed and demonstrated. The singlet oxygen photosensitizer pyropheophorbide-a (P) was attached to a 15-mer nucleotide sequence. A molecule that could quench the sensitizer, the so-called "black hole quencher 3" (Q), was attached to a complementary nucleotide strand. Upon hybridization of the two conjugates, singlet oxygen production from P was completely shut down. Upon the addition of a third DNA sequence that can displace and release the P-DNA conjugate from the P-Q pair, up to 85% of the singlet oxygen production was recovered. This system is a model for a benign drug that becomes active only in the presence of a specific targeted nucleotide sequence.

Characterization of 43 Non-Protein-Coding mRNA Genes in Arabidopsis, Including the MIR162a-Derived Transcripts

Messenger RNAs that do not contain a long open reading frame (ORF) or non-protein-coding RNAs (npcRNAs) are an emerging novel class of transcripts. Their functions may involve the RNA molecule itself and/or short ORF-encoded peptides. npcRNA genes are difficult to identify using standard gene prediction programs that rely on the presence of relatively long ORFs. Here, we used detailed bioinformatic analyses of expressed sequence tag/cDNA databases to detect a restricted set of npcRNAs in the Arabidopsis (Arabidopsis thaliana) genome and further characterized these transcripts using a combination of bioinformatic and molecular approaches. Compositional analyses revealed strong nucleotide strand asymmetries in the npcRNAs, as well as a biased GC content, suggesting the existence of functional constraints on these RNAs. Thirteen of these transcripts display tissue-specific expression patterns, and three are regulated in conditions affecting root architecture. The npcRNA 78 gene contains the miR162 sequence in an alternative intron and corresponds to the MIR162a locus. Although DICER-LIKE 1 (DCL1) mRNA is known to be regulated by miR162-guided cleavage, its level does not change in a mir162a mutant. Alternative splicing of npcRNA 78 leads to several transcript isoforms, which all accumulate in a dcl1 mutant. This suggests that npcRNA 78 is a genuine substrate of DCL1 and that splicing of this microRNA primary transcript and miR162 processing are competitive nuclear events. Our results provide new insights into Arabidopsis npcRNA biology and the potential roles of these genes.

Tetranucleotides as a scaffold for diporphyrin arrays

The incorporation of porphyrin-substituted nucleosides into tetranucleotides using phosphoramidite chemistry on solid support is reported. Both diphenyl and tetraphenyl porphyrin nucleosides were used as building blocks. This method allows the synthesis of chiral homo- and heteroporphyrinic arrays, where the composition and thus the physical properties of the array can be modulated simply by reprogramming the DNA synthesizer. The porphyrin arrays are initially isolated in the free-base form. Remetallation to give the zinc-porphyrins can be achieved using standard procedures in solution. The UV-vis spectra of the arrays are reproducible by a superposition of the absorbance spectra of the individual porphyrins, indicating an undisturbed electronic ground state of the porphyrins in the arrays. The same is true for the steady-state emission spectra of the homoporphyrinic arrays, which are not influenced by the presence of the nucleotide strand. In the mixed porphyrin arrays, large differences in the excited-state properties compared to an equimolar mixture of the building blocks are observed by means that the emission of the diphenyl porphyrin moiety is quenched to a large extent, and the overall emission is dominated by the tetraphenyl porphyrin. The covalent connection of the porphyrins via the DNA-derived backbone therefore substantially alters the excited-state and energy-transfer properties of mixed porphyrin systems. The circular dichroism (CD) spectra show induced negative cotton effects in the region of the porphyrin B-band absorption, which is due to the attachment of the chromophores to the chiral oligonucleotide backbone. Addition of a complementary tetra-adenosine did not alter any of the spectroscopic properties, neither in chloroform nor in acetonitrile solutions. Therefore, it can be concluded that no duplex is formed, which is corroborated by 1H NMR spectroscopy.

Electromagnetic field effect on separation of nucleotide sequences and unwinding of a double helix during DNA replication

Our previous pre-clinic experimental results have showed that the bacterium infection can be suppressed and the epithelialization can be enhanced by the externally applied rectangular pulsed electrical current stimulation (RPECS). The results are clinically significant for patients, especially for those difficult patients whose skin wounds need long periods to heal. However, the results also raise questions: How does the RPECS accelerate the epithelium cell proliferation? What is the relationship among the bacterium infection, the epithelialization and the RPECS? To answer these questions, we have previously modeled mitosis and cytokinesis mechanisms for animal cells and amitosis for bacteria at a cellular level and in a view of physics. In this paper, we model the separation of nucleotide sequences and the unwinding of a double helix during DNA replication at a molecular level and also in wild types of cells. Firstly, we define a new concept of nucleotide (NT) electromagnetic field (EMF) box (sequence) which carries genetic information: The continuous NT EMF boxes compose a nucleotide strand. Then, we hypothesize the symmetry, repulsion and attraction of NT EMF boxes: If a pair of NT EMF boxes are (quasi) mirror or complementary symmetric about a plane (curve) or point, they repulse or attract from each other because there is a repulsive or attractive EMF force between them. Our models suggest, the repulsive EMF force from children DNA strands simultaneously separates the children DNA strands, splits the hydrogen bonds of parental base pairs, and unwinds the parental double helix while DNA polymerases are synchronously synthesizing the new children DNA strands. To understand the mechanism of epithelialization enhanced with the externally applied RPECS at a molecular level, we hypothesize that the normal separation of nucleotide sequences and unwinding of a double helix during DNA replication could be suppressed in the bacteria but not in the epithelium cells because: (a) the spontaneous EMF in the epithelium could be 1000 times stronger than that in bacteria; (b) the epithelium cells have one more non-conducting envelope (nuclear membrane) to protect the normal separation and unwinding; (c) based on our previous experimental data, the RPECS amount received by the bacteria are three times as much as the amount the epithelium cells receive. Therefore, the epithelium cellular proliferation may be directly, as well as indirectly (e.g., somatic reflex) accelerated by the RPECS.

Genome-wide selection of unique and valid oligonucleotides

Functional genomics methods are used to investigate the huge amount of information contained in genomes. Numerous experimental methods rely on the use of oligo- or polynucleotides. Nucleotide strand hybridization forms the underlying principle for these methods. For all these techniques, the probes should be unique for analyzed genes. In addition to being unique for the studied genes, the probes should fulfill a large number of criteria to be usable and valid. The criteria include for example, avoidance of self-annealing, suitable melting temperature and nucleotide composition. We developed a method for searching unique and valid oligonucleotides or probes for genes so that there is not even a similar (approximate) occurrence in any other location of the whole genome. By using probe size 25, we analyzed 17 complete genomes representing a wide range of both prokaryotic and eukaryotic organisms. More than 92% of all the genes in the investigated genomes contained valid oligonucleotides. Extensive statistical tests were performed to characterize the properties of unique and valid oligonucleotides. Unique and valid oligonucleotides were relatively evenly distributed in genes except for the beginning and end, which were somewhat overrepresented. The flanking regions in eukaryotes were clearly underrepresented among suitable oligonucleotides. In addition to distributions within genes, the effects on codon and amino acid usage were also studied.

Entrapment of Fluorescent Signaling DNA Aptamers in Sol−Gel-Derived Silica

We report on the first successful immobilization of a DNA aptamer, in particular, a fluorescence-signaling DNA aptamer, within a sol-gel-derived matrix. The specific aptamer examined in this study undergoes a structural switch in the presence of adenosine triphosphate (ATP) to release a dabcyl-labeled nucleotide strand (QDNA), which in turn relieves the quenching of a fluorescein label that is also present in the aptamer structure. It was demonstrated that aptamers containing a complementary QDNA strand along with either a short complimentary strand bearing fluorescein (tripartite structure) or a directly bound fluorescein moiety (bipartite structure) remained intact upon entrapment within biocompatible sol-gel derived materials and retained binding activity, structure-switching capabilities, and fluorescence signal generation that was selective and sensitive to ATP concentration. Studies were undertaken to evaluate the properties of the immobilized aptamers that were either in their native state or bound to streptavidin using a terminal biotin group on the aptamer, including response time, accessibility, and leaching. Furthermore, signaling abilities were optimized through evaluation of different QDNA constructs. These studies indicated that the aptamers remained in a state that was similar to solution, with moderate leaching, only minor decreases in accessibility to ATP, and an expected reduction in response time due to diffusional barriers to mass transport of the analyte through the silica matrix. Entrapment of the aptamer also resulted in protection of the DNA against degradation from nucleases, improving the potential for use of the aptamer for in vivo sensing. This work demonstrates that sol-gel-derived materials can be used to successfully immobilize and protect DNA-based biorecognition elements and, in particular, DNA aptamers, opening new possibilities for the development of DNA aptamer-based devices, such as affinity columns, microarrays, and fiber-optic sensors.

Molecular analysis suggests that recent Citrus tristeza virus outbreaks in Italy were originated by at least two independent introductions

Citrus tristeza virus (CTV) is the causal agent of the most important virus disease of citrus. Numerous CTV isolates differing in biological and molecular characteristics have been reported worldwide. Recently, CTV was detected in Italy in several citrus crops from three separate areas: (1) Cassibile, province of Syracuse; (2) Massafra, province of Taranto; and (3) Belpasso, province of Catania. CTV isolates from Massafra and Cassibile were mild, whereas isolates from Belpasso induced severe symptoms. To study the genetic variation of CTV populations of these areas, 150 samples per area were examined by single strand conformation polymorphism (SSCP) and nucleotide sequence analysis of CTV gene p20. All isolates from the same area showed the same SSCP pattern whereas for each area a different SSCP pattern was obtained. The Massafra and the Cassibile isolates had a nucleotide identity higher than 99% with a mild isolate from Spain and about 92% with the Belpasso isolates, which were similar (identity higher than 99%) to severe isolates from California and Japan. These results suggest at least two independent introductions of CTV in Italy, probably by import of CTV-infected budwoods. Within each area, the virus population was homogeneous suggesting diffusion of CTV by aphid transmission.

Rare Mutations of the PIK3CA Gene in Hematologic Malignancies.

Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that is activated in advanced cancers through inactivation of the PTEN tumor suppressor gene. Somatic mutations in the p110-alpha catalytic subunit, PIK3CA occur in colon, gastric, breast and lung cancers as well as in glioblastomas and colorectal adenomas. Mutations were found in two “hot spots”: the helical (exon 9) and kinase (exon 20) domains. Mutational analysis of PIK3CA in hematologic malignancies has not been reported. We performed a screening analysis of 28 cell lines from human hematologic malignancies as well as 46 AML and MDS samples and 42 lymphoma samples by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and nucleotide sequencing of the two “hot spots”. Two colon adenocarcinoma cell lines (SKCol1, SW403) were used as positive controls and revealed the known missense mutation (Q546K) in exon 9. A novel missense mutation occurred in the erythroid chronic myeloid leukemia cell line K562, causing an amino acid change from Glutamic acid to Alanine at amino acid position 545 of exon 9 (E545A). In the kinase domain (exon 20), a novel polymorphism was observed in two different MDS patients at Threonine residue 1025. Experiments are exploring the functional importance of the PIK3CA mutation and the PIK3CA polymorphism in exon 20. In summary, PIK3CA mutations are infrequent in hematologic malignancies.

Maternal heterozygosity for a mitochondrial trifunctional protein mutation as a cause for liver disease in pregnancy

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are serious complications of pregnancy associated with significant maternal and perinatal morbidity and mortality. In previous reports, we have documented an association between AFLP and fetal deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) [N. Engl. J. Med. 340 (1999) 1723-1731; JAMA 288 (2002) 2163-2166]. LCHAD activity resides in the alpha-subunit of the mitochondrial trifunctional protein (MTP), a complex protein that catalyzes beta-oxidation of long chain fatty acids. In all reported cases, the fetus carried a common alpha-subunit MTP mutation (G1528C, E474Q) on one or both alleles. However, the association between fetal LCHAD deficiency and the maternal HELLP syndrome has been limited. Here, we report a case history of a 27-year-old black female who underwent Cesarean section for placenta previa and fetal distress at 36 weeks gestation. The newborn was a healthy male child. Post-delivery, the mother developed severe HELLP syndrome with complications resulting in death of the patient. We used single strand conformation variance and nucleotide sequence analyses to screen DNA isolated from the mother and the newborn for mutations in the MTP alpha-subunit. The mother was heterozygous for a novel mutation (C1072A, Q322K) in exon 11 of the LCHAD domain of the MTP, while the fetal genotype was completely normal. We hypothesize that, in some cases, maternal heterozygosity for an MTP mutation maybe sufficient to cause the development of maternal liver disease without carrying an affected fetus. Combination of the metabolic stress of pregnancy and other environmental stresses may overwhelm the heterozygous mother's capacity for effective metabolism of long chain fatty acids, leading to an accumulation of potentially toxic fatty acid metabolites in the maternal circulation with subsequent damage to the maternal liver.

Cathepsin S supports acid-independent infection by some reoviruses.

In murine fibroblasts, efficient proteolysis of reovirus outer capsid protein sigma3 during cell entry by virions requires the acid-dependent lysosomal cysteine protease cathepsin L. The importance of cathepsin L for infection of other cell types is unknown. Here we report that the acid-independent lysosomal cysteine protease cathepsin S mediates outer capsid processing in macrophage-like P388D cells. P388D cells supported infection by virions of strain Lang, but not strain c43. Genetic studies revealed that this difference is determined by S4, the viral gene segment that encodes sigma3. c43-derived subvirion particles that lack sigma3 replicated normally in P388D cells, suggesting that the difference in infectivity of Lang and c43 virions is at the level of sigma3 processing. Infection of P388D cells with Lang virions was inhibited by the broad spectrum cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido-(4-guanidino)butane but not by NH(4)Cl, which raises the endocytic pH and thereby inhibits acid-dependent proteases such as cathepsins L and B. Outer capsid processing and infection of P388D cells with Lang virions were also inhibited by a cathepsin S-specific inhibitor. Furthermore, in the presence of NH(4)Cl, cell lines engineered to express cathepsin S supported infection by Lang, but not c43, virions. Our results thus indicate that differences in susceptibility to cathepsin S-mediated sigma3 processing are responsible for strain differences in reovirus infection of macrophage-like P388D cells and other cathepsin S-expressing cells. Additionally, our data suggest that the acid dependence of reovirus infections of most other cell types may reflect the low pH requirement for the activities of most other lysosomal proteases rather, than some other acid-dependent aspect of cell entry.

A quantitative method to detect HBV cccDNA by chimeric primer and real-time polymerase chain reaction

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), is a continuous double chain ring, while other DNA forms contain a gap on each chain at the position of direct repeat 1 sequence (DR1) and direct repeat 2 sequence (DR2), respectively. At present it is still difficult to detect with high sensitivity and specificity and quantify the HBV cccDNA pool in the nucleus of the hepatocyte. A chimeric primer was designated in which segment A near 3′ end is complementary to HBV plus strand just before the DR2 region gap, and segment B near 5′ end is consensus to part of the human immunodefficient virus genomic sequence, without homogenetic relationship to HBV genome. Promoted by taq DNA polymerase, a single nucleotide strand is elongated from chimeric primer generated by HBV cccDNA. In contrast, other HBV DNA forms do not produce a single nucleotide strand due to the cessation of elongation reaction at the DR2 gap. The newly formed single nucleotide strand is subsequently amplified by a new polymerase chain reaction system (PCR), in which a primer, identical to chimeric primer segments B, is used to ensure specific amplification, avoiding other HBV DNA format inference. In addition, a taqman probe was used in the PCR system to report the detection signal, and for constructing a standard curve between cycle threshold (Ct) value and the template quantity. This technique proved to be effective for rapid and sensitive detection and quantitation of HBV cccDNA with high specificity and efficacy.

P53 and PTEN/MMAC1 mutational analysis of the small-intestinal cancer

A 66-year-old female, suffering from small-intestinal cancer underwent resection of the small intestine. Genome DNAs were extracted from the patient's blood and small-intestinal cancer and were subjected to a polymerase chain reaction-single strand conformation polymorphism and nucleotide sequence analysis for exons of the p53 and PTEN/MMAC1 genes to search for any mutations. The sequence analysis revealed a point mutation of the p53 codon 93 in the cancer DNA; however, no mutation of the PTEN/MMAC1 gene was observed in either the blood or cancer DNA. The p53 mutation, therefore, seems to be related to tumour progression of small-intestinal cancer; however, no relationship was found between the PTEN/MMAC1 gene and the small-intestinal cancer.

Identification of Th2-type suppressor T cells among in vivo expanded ocular T cells in mice with experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU), which is a T cell mediated organ specific autoimmune disease, is induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in susceptible strains of mice. It has been found that IRBP-derived peptide 518-529 (p518-529) generates Th2-type responses and inhibits IRBP-induced EAU, indicating that the p518-529 might be an epitope for suppressor T cells in IRBP-induced EAU. First, we observed that there were T cells producing the Th2 type cytokines such as IL-4 and IL-10 in late phase of EAU. Furthermore, to examine whether p518-529-reactive T cells expand in the eye during EAU, T cell receptor (TCR) of ocular T cells was compared with that of p518-529 reactive T cells in spleen from mice with EAU by PCR-single strand conformation polymorphism (PCR-SSCP) and nucleotide sequence analysis. SSCP and sequence analyses indicated that p518-529 reactive TCR BV10+ T cells bearing amino acid motif(PWG) and TCR BV13+ T cells bearing amino acid motif(PGLGGY) in their complementary-determining region 3 (CDR3) region were clonally expanding in ocular tissues on day 28 after immunization, although these T cells were not detected on day 14. These findings demonstrate that p518-529 reactive Th2-type T cells expand oligoclonally in the uveitic eyes in the late stage of EAU and may function as Th2-type suppressor T cells for improvement of the disease.

Laboratory assessment of transthyretin amyloidosis.

Mutations in transthyretin (TTR) are the most common cause of autosomal dominant systemic amyloidosis. To date, more than 80 TTR mutations have been associated with amyloidosis in humans. A high prevalence of some mutations like Val122Ile which is identified in 3% of African Americans indicates the necessity of thorough investigation of patients suspected of having, or to be at risk of developing, TTR amyloidosis. Laboratory tests available for evaluation of TTR amyloidosis include both DNA and protein assays. In the case of a known mutation DNA analysis is realized by restriction fragment length polymorphism (RFLP), polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA), single strand confirmation polymorpism (SSCP) or nucleotide sequencing. SSCP, PCR-non-isotopic RNAse cleavage assay (NIRCA) or nucleotide sequencing are used to identify an unknown mutation. At the protein level, two techniques are used, isoelectric focusing and mass spectrometry, in both cases (known or unknown mutation). The identification of a previously unknown mutation requires a combination of clinical, pathological and molecular studies.

One hour, one genome

Using a novel sequencing method, Harvard University researchers aim to reduce the time taken to sequence a genome to a matter of hours [Wang and Branton (2001) Nat. Biotechnol. 19, 622–623]. Sequencing the genome took the public consortium more than a decade, and the Celera biotechnology company approximately nine months (with input from the public project). The novel method, developed by Daniel Branton and Jene Golovchenko of Harvard University (Cambridge, MA, USA), together with David Deamer of the University of California (CA, USA), uses a lipid bilayer to compartmentalize a dish into two separate regions. A long single strand of (negatively charged) nucleotides is placed on one side of the bilayer. Application of α-hemolysin causes formation of a nanopore in the membrane, across which a voltage bias is then applied. The nucleotide chain worms its way through the channel towards the positive side of the dish, such that each nucleotide flowing through the nanopore generates a distinct current. The nucleotides can pass through the channel pore only in sequential, single-file order because the limiting diameter of the pore (∼1.5 nm) can accommodate only one strand of DNA or RNA at a time. Very small changes in the distribution of charges within the channel can give rise to very large changes in the ionic flux through the channel pore. The aim is that each nucleotide will be identified, and the polynucleotide chain therefore sequenced, during this translocation. Difficulties to be overcome include slowing down the movement of the chain through the pore so that the electronic detector can record the individual bases moving past. In addition, computer algorithms that can process the volume of data resulting from scanning up to 70 000 nucleotides in a matter of minutes need to be developed. S de B (http://www.economist.com/science/tq/displayStory.cfm?Story_ID=662230&CFID=1206325&CFTOKEN=54743604; http://golgi.harvard.edu/branton/nanopore.html)

Force and kinetic barriers to unzipping of the DNA double helix.

A theory of the unzipping of double-stranded DNA is presented and is compared to recent micromanipulation experiments. It is shown that the interactions that stabilize the double helix and the elastic rigidity of single strands simply determine the sequence-dependent approximately 12-pN force threshold for DNA strand separation. Using a semimicroscopic model of the binding between nucleotide strands, we show that the greater rigidity of the strands when formed into double-stranded DNA, relative to that of isolated strands, gives rise to a potential barrier to unzipping. The effects of this barrier are derived analytically. The force to keep the extremities of the molecule at a fixed distance, the kinetic rates for strand unpairing at fixed applied force, and the rupture force as a function of loading rate are calculated. The dependence of the kinetics and of the rupture force on molecule length is also analyzed.

Array of hope for gene technology.

A Washington-based bioinformatics company is developing sophisticated DNA microarrays that should help researchers measure and analyze gene expression faster, more economically, and with greater precision than ever before possible. The FlexJet system, as the microarray product is known, uses inkjet technology to propel microscopic strands of DNA nucleotides onto slides, "printing" arrays of DNA molecules in a process not unlike the manner in which a printer deposits ink onto paper, forming distinct patterns of characters and images. Microarray technology may revolutionize the field of toxicogenomics by helping scientists target new drugs, discover gene function, determine biologic pathways, and better understand diseases such as cancer, cystic fibrosis, and cardiovascular disease at the molecular level.

Array of Hope for Gene Technology

A Washington-based bioinformatics company is developing sophisticated DNA microarrays that should help researchers measure and analyze gene expression faster, more economically, and with greater precision than ever before possible. The FlexJet system, as the microarray product is known, uses inkjet technology to propel microscopic strands of DNA nucleotides onto slides,