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Terms and Definitions

Antisense oligonucleotide

Antisense oligonucleotides are single strands of DNA or RNA (or modified variants thereof) that are complementary to a chosen sequence. Cylene is not developing oligonucleotides as product candidates, but rather creates small molecule drugs.

Antisense therapy

Antisense molecules interact with complementary strands of nucleic acids, modifying expression of genes. Antisense therapy is a theoretical form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind to the messenger RNA (mRNA) produced by that gene, effectively turning that gene "off". This synthesized nucleic acid is termed an "anti-sense" oligonucleotide because its base sequence is complementary to the gene's mRNA, which is called the "sense" sequence.

Apoptosis

A process of deliberate life relinquishment by an unwanted cell in a multicellular organism. In contrast to necrosis, which is a form of cell death that results from acute cellular injury, apoptosis is carried out in an ordered process that generally confers advantages during an organism's life cycle. Excessive apoptosis causes cell-loss disorders, whereas insufficient apoptosis results in uncontrolled cell proliferation, namely cancerous tumors.

G-Quadruplex

Higher-order DNA structures comprising four DNA strands with a core motif of hydrogen-bonded Guanines in a tetrad arrangement. G-quadruplex motifs are found throughout the human genome, particularly in the telomeres and ribosomal DNA and other recombination hot spots.

Kinases

Kinases are enzymes that transfer phosphate groups onto specific substrates. The largest group of kinases encompasses protein kinases. These protein kinases phosphylate specific proteins and are used extensively to transmit signals and control complex processes in cells.

Kinase Inhibitors

Any substance or agent which suppresses, prevents or opposes the action of protein kinase enzymes.

Nucleolar Hypertrophy

Highly enlarged nucleoli, which are characteristic features of cancer cells and are utilized by pathologists for cancer diagnosis.

Nucleolin

A protein that is abundant in the nucleolus and that is absolutely essential for ribosomal RNA biogenesis and other cellular processes. Nucleolar proteins structurally related to nucleolin are found in organisms ranging from yeast to plants and mammals. The association of several structural domains in nucleolin allows the interaction of nucleolin with different proteins and nucleic acid sequences.

Nucleolus

Nucleoli (plural) are dynamic ribosome factories that coalesce within the nucleus around the tandem repeats of rRNA genes found on the acrocentric chromosomes. Nucleoli form as non-membrane-bound regions within the nucleus. Abnormally large and overly abundant nucleoli are hallmarks of cancer cells.

Ribosome

An organelle composed of RNA and ribosomal proteins (known as a Ribonucleoprotein or RNP). It translates messenger RNA (mRNA) into a polypeptide chain (e.g., a protein). It can be thought of as a factory that builds proteins from a set of genetic instructions.

Ribosome Biogenesis

The assembly, as well as the synthesis and processing, of various RNA and protein components into functional ribosomal subunits, followed by their export to the sites of protein synthesis.

Ribosomal DNA (rDNA)

A class of DNA that consists of 400-500 copies of the rRNA genes. These copies are found on the short arms of acrocentric chromosomes, which coalesce into the nucleolus.

Ribosomal RNA (rRNA)

rRNA genes give rise to precursor-ribosomal RNA that is subsequently processed to the mature 18S, 5.8S, and 28S, rRNA entities. These mature rRNAs represent major building blocks for ribosomes.

Ribosomal RNA (rRNA) Biogenesis

A process in which the rRNA genes are transcribed by the RNA Polymerase I (Pol I) enzyme to synthesize precursor-rRNA strands, and the subsequent processing of the pre-rRNA into mature 28S, 5.8S, and 18S rRNA units.

RNA Polymerase I (Pol I)

An enzyme responsible for transcribing the rRNA genes of rDNA to create full length strands of precursor-rRNA. The Pol I enzyme is a key enzymatic component of the functional pre-initiation complex (PIC), which consists of numerous proteins that act in concert to execute rRNA synthesis.

Tumor Suppressor Proteins

Tumor suppressor proteins have a repressive effect on the cell cycle or promote apoptosis. Examples include the p53 and RB proteins, and these proteins modify various proteins within the PIC and thereby down-regulate rRNA synthesis and resultant protein synthesis and cell growth.


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