Food and Drug Administration
The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements and over-the-counter pharmaceutical drugs, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, animal foods & feed and veterinary products; as of 2017, 3/4th of the FDA budget is paid by people who consume pharmaceutical products, due to the Prescription Drug User Fee Act. The FDA was empowered by the United States Congress to enforce the Federal Food and Cosmetic Act, which serves as the primary focus for the Agency; these include regulating lasers, cellular phones and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate.
The Commissioner reports to the Secretary of Human Services. Scott Gottlieb, M. D. is the current commissioner, who took over in May 2017. The FDA has its headquarters in Maryland; the agency has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, Puerto Rico. In 2008, the FDA began to post employees to foreign countries, including China, Costa Rica, Chile and the United Kingdom. In recent years, the agency began undertaking a large-scale effort to consolidate its 25 operations in the Washington metropolitan area, moving from its main headquarters in Rockville and several fragmented office buildings to the former site of the Naval Ordnance Laboratory in the White Oak area of Silver Spring, Maryland; the site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the naval facility was kept.
All other buildings are new construction. The project is slated to be completed by 2021, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. area as part of the Headquarters divisions, two offices – the Office of Regulatory Affairs and the Office of Criminal Investigations – are field offices with a workforce spread across the country. The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field. Consumer Safety Officers, more called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, review documentation in the case of medical devices, biological products, other items where it may be difficult to conduct a physical examination or take a physical sample of the product; the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based on the geographic divisions of the federal court system.
Each district comprises a main district office and a number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA includes the Agency's network of regulatory laboratories, which analyze any physical samples taken. Though samples are food-related, some laboratories are equipped to analyze drugs and radiation-emitting devices; the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, don't focus on technical aspects of the regulated industries. OCI agents pursue and develop cases where individuals and companies have committed criminal actions, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving Title 18 violations, in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents come from other criminal investigations backgrounds, work with the Federal Bureau of Investigation, Assistant Attorney General, Interpol.
OCI receives cases from a variety of sources—including ORA, local agencies, the FBI—and works with ORA Investigators to help develop the technical and science-based aspects of a case. OCI is a smaller branch; the FDA works with other federal agencies, including the Department of Agriculture, Drug Enforcement Administration and Border Protection, Consumer Product Safety Commission. Local and state government agencies work with the FDA to provide regulatory inspections and enforcement action; the FDA regulates more than US$2.4 trillion worth of consumer goods, about 25% of consumer expenditures in the United States. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. Much of these expenditures are for goods imported into the United States; the FDA's federal budget request for fiscal year 2012 totaled $4.36 billion, while the proposed 2014 budget is $4.7 billion. About $2 billion of this budget is generated by user fees.
Pharmaceutical firms pay th
Nucleic acid sequence
A nucleic acid sequence is a succession of letters that indicate the order of nucleotides forming alleles within a DNA or RNA molecule. By convention, sequences are presented from the 5' end to the 3' end. For DNA, the sense strand is used; because nucleic acids are linear polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is termed the primary structure; the sequence has capacity to represent information. Biological deoxyribonucleic acid represents the information which directs the functions of a living thing. Nucleic acids have a secondary structure and tertiary structure. Primary structure is sometimes mistakenly referred to as primary sequence. Conversely, there is no parallel concept of tertiary sequence. Nucleic acids consist of a chain of linked units called nucleotides; each nucleotide consists of three subunits: a phosphate group and a sugar make up the backbone of the nucleic acid strand, attached to the sugar is one of a set of nucleobases.
The nucleobases are important in base pairing of strands to form higher-level secondary and tertiary structure such as the famed double helix. The possible letters are A, C, G, T, representing the four nucleotide bases of a DNA strand — adenine, guanine, thymine — covalently linked to a phosphodiester backbone. In the typical case, the sequences are printed abutting one another without gaps, as in the sequence AAAGTCTGAC, read left to right in the 5' to 3' direction. With regards to transcription, a sequence is on the coding strand if it has the same order as the transcribed RNA. One sequence can be complementary to another sequence, meaning that they have the base on each position in the complementary and in the reverse order. For example, the complementary sequence to TTAC is GTAA. If one strand of the double-stranded DNA is considered the sense strand the other strand, considered the antisense strand, will have the complementary sequence to the sense strand. Comparing and determining % difference between two nucleotide sequences.
AATCCGCTAG AAACCCTTAG Given the two 10-nucleotide sequences, line them up and compare the differences between them. Calculate the percent similarity by taking the number of different DNA bases divided by the total number of nucleotides. In the above case, there are three differences in the 10 nucleotide sequence. Therefore, divide 7/10 to get the 70% similarity and subtract that from 100% to get a 30% difference. While A, T, C, G represent a particular nucleotide at a position, there are letters that represent ambiguity which are used when more than one kind of nucleotide could occur at that position; the rules of the International Union of Pure and Applied Chemistry are as follows: These symbols are valid for RNA, except with U replacing T. Apart from adenine, guanine and uracil, DNA and RNA contain bases that have been modified after the nucleic acid chain has been formed. In DNA, the most common modified base is 5-methylcytidine. In RNA, there are many modified bases, including pseudouridine, inosine, ribothymidine and 7-methylguanosine.
Hypoxanthine and xanthine are two of the many bases created through mutagen presence, both of them through deamination. Hypoxanthine is produced from adenine, xanthine is produced from guanine. Deamination of cytosine results in uracil. In biological systems, nucleic acids contain information, used by a living cell to construct specific proteins; the sequence of nucleobases on a nucleic acid strand is translated by cell machinery into a sequence of amino acids making up a protein strand. Each group of three bases, called a codon, corresponds to a single amino acid, there is a specific genetic code by which each possible combination of three bases corresponds to a specific amino acid; the central dogma of molecular biology outlines the mechanism by which proteins are constructed using information contained in nucleic acids. DNA is transcribed into mRNA molecules, which travels to the ribosome where the mRNA is used as a template for the construction of the protein strand. Since nucleic acids can bind to molecules with complementary sequences, there is a distinction between "sense" sequences which code for proteins, the complementary "antisense" sequence, by itself nonfunctional, but can bind to the sense strand.
DNA sequencing is the process of determining the nucleotide sequence of a given DNA fragment. The sequence of the DNA of a living thing encodes the necessary information for that living thing to survive and reproduce. Therefore, determining the sequence is useful in fundamental research into why and how organisms live, as well as in applied subjects; because of the importance of DNA to living things, knowledge of a DNA sequence may be useful in any biological research. For example, in medicine it can be used to identify and develop treatments for genetic diseases. Research into pathogens may lead to treatments for contagious diseases. Biotechnology is a burgeoning discipline, with the potential for services. RNA is not sequenced directly. Instead, it is copied to a DNA by reverse transcriptase, this DNA is sequenced. Current sequencing methods rely on the discriminatory ability of DNA polymerases, therefore can only distinguish four bases. An inosine is read as a G, 5-methyl-cytosine is read as a C.
A Morpholino known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer, is a type of oligomer molecule used in molecular biology to modify gene expression. Its molecular structure has DNA bases attached to a backbone of methylenemorpholine rings linked through phosphorodiamidate groups. Morpholinos block access of other molecules to small specific sequences of the base-pairing surfaces of ribonucleic acid. Morpholinos are used as research tools for reverse genetics by knocking down gene function; this article discusses only the Morpholino antisense oligomers. The word "Morpholino" can occur in other chemical names, referring to chemicals containing a six-membered morpholine ring. To help avoid confusion with other morpholine-containing molecules, when describing oligos "Morpholino" is capitalized as a trade name, but this usage is not consistent across scientific literature. Morpholino oligos are sometimes referred to as PMO in medical literature. Vivo-Morpholinos and PPMO are modified forms of Morpholinos with chemical groups covalently attached to facilitate entry into cells.
Gene knockdown is achieved by preventing cells from making a targeted protein. Knocking down gene expression is a method for learning about the function of a particular protein; these molecules have been applied to studies in several model organisms, including mice, zebrafish and sea urchins. Morpholinos can modify the splicing of pre-mRNA or inhibit the maturation and activity of miRNA. Techniques for targeting Morpholinos to RNAs and delivering Morpholinos into cells have been reviewed in a journal article and in book form. Morpholinos are in development as pharmaceutical therapeutics targeted against pathogenic organisms such as bacteria or viruses and genetic diseases; the Morpholino drug eteplirsen from Sarepta Therapeutics received accelerated approval from the US Food and Drug Administration for treatment of some mutations causing Duchenne muscular dystrophy. Morpholino oligos were conceived by Summerton at AntiVirals Inc. and developed in collaboration with Weller. Morpholinos are synthetic molecules that are the product of a redesign of natural nucleic acid structure.
25 bases in length, they bind to complementary sequences of RNA or single-stranded DNA by standard nucleic acid base-pairing. In terms of structure, the difference between Morpholinos and DNA is that, while Morpholinos have standard nucleic acid bases, those bases are bound to methylenemorpholine rings linked through phosphorodiamidate groups instead of phosphates; the figure compares the structures of the two strands depicted there, one of RNA and the other of a Morpholino. Replacement of anionic phosphates with the uncharged phosphorodiamidate groups eliminates ionization in the usual physiological pH range, so Morpholinos in organisms or cells are uncharged molecules; the entire backbone of a Morpholino is made from these modified subunits. Morpholinos do not trigger the degradation of their target RNA molecules, unlike many antisense structural types. Instead, Morpholinos act by "steric blocking", binding to a target sequence within an RNA, inhibiting molecules that might otherwise interact with the RNA.
Morpholino oligos are used to investigate the role of a specific mRNA transcript in an embryo. Developmental biologists inject Morpholino oligos into eggs or embryos of zebrafish, African clawed frog, sea urchin and killifish producing morphant embryos, or electroporate Morpholinos into chick embryos at development stages. With appropriate cytosolic delivery systems, Morpholinos are effective in cell culture. Vivo-Morpholinos, in which the oligo is covalently linked to a delivery dendrimer, enter cells when administered systemically in adult animals or in tissue cultures. In eukaryotic organisms, pre-mRNA is transcribed in the nucleus, introns are spliced out the mature mRNA is exported from the nucleus to the cytoplasm; the small subunit of the ribosome starts by binding at the 5' end end of the mRNA and is joined there by various other eukaryotic initiation factors, forming the initiation complex. The initiation complex scans along the mRNA strand until it reaches a start codon, the large subunit of the ribosome attaches to the small subunit and translation of a protein begins.
This entire process is referred to as gene expression. A Morpholino can modify splicing, block translation, or block other functional sites on RNA depending on the Morpholino's base sequence. Bound to the 5'-untranslated region of messenger RNA, Morpholinos can interfere with progression of the ribosomal initiation complex from the 5' cap to the start codon; this prevents translation of the coding region of the targeted transcript. This is useful experimentally when an investigator wishes to know the function of a particular protein; some Morpholinos knock down expression so that, after degradation of preexisting proteins, the targeted proteins become undetectable by Western blot. In 2016 a synthetic peptide-conjugated PMO was found to
RNA interference is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. RNAi was known by other names, including co-suppression, post-transcriptional gene silencing, quelling; the detailed study of each of these different processes elucidated that the identity of these phenomena were all RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient and better than antisense technology for gene suppression. However, antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents. Two types of small ribonucleic acid molecules – microRNA and small interfering RNA – are central to RNA interference.
RNAs are the direct products of genes, these small RNAs can direct enzyme complexes to degrade messenger RNA molecules and thus decrease their activity by preventing translation, via post-transcriptional gene silencing. Moreover, transcription can be inhibited via the pre-transcriptional silencing mechanism of RNA interference, through which an enzyme complex catalyzes DNA methylation at genomic positions complementary to complexed siRNA or miRNA. RNA interference has an important role in defending cells against parasitic nucleotide sequences – viruses and transposons, it influences development. The RNAi pathway is found in many eukaryotes, including animals, is initiated by the enzyme Dicer, which cleaves long double-stranded RNA molecules into short double-stranded fragments of ~21 nucleotide siRNAs; each siRNA is unwound into the passenger strand and the guide strand. The passenger strand is degraded and the guide strand is incorporated into the RNA-induced silencing complex; the most well-studied outcome is post-transcriptional gene silencing, which occurs when the guide strand pairs with a complementary sequence in a messenger RNA molecule and induces cleavage by Argonaute 2, the catalytic component of the RISC.
In some organisms, this process spreads systemically, despite the limited molar concentrations of siRNA. RNAi is a valuable research tool, both in cell culture and in living organisms, because synthetic dsRNA introduced into cells can selectively and robustly induce suppression of specific genes of interest. RNAi may be used for large-scale screens that systematically shut down each gene in the cell, which can help to identify the components necessary for a particular cellular process or an event such as cell division; the pathway is used as a practical tool in biotechnology and insecticides. RNAi is RNA-dependent gene silencing process, controlled by the RNA-induced silencing complex and is initiated by short double-stranded RNA molecules in a cell's cytoplasm, where they interact with the catalytic RISC component argonaute; when the dsRNA is exogenous, the RNA is imported directly into the cytoplasm and cleaved to short fragments by Dicer. The initiating dsRNA can be endogenous, as in pre-microRNAs expressed from RNA-coding genes in the genome.
The primary transcripts from such genes are first processed to form the characteristic stem-loop structure of pre-miRNA in the nucleus exported to the cytoplasm. Thus, the two dsRNA pathways and endogenous, converge at the RISC. Exogenous dsRNA initiates RNAi by activating the ribonuclease protein Dicer, which binds and cleaves double-stranded RNAs in plants, or short hairpin RNAs in humans, to produce double-stranded fragments of 20–25 base pairs with a 2-nucleotide overhang at the 3' end. Bioinformatics studies on the genomes of multiple organisms suggest this length maximizes target-gene specificity and minimizes non-specific effects; these short double-stranded fragments are called small interfering RNAs. These siRNAs are separated into single strands and integrated into an active RISC, by RISC-Loading Complex. RLC includes Dicer-2 and R2D2, is crucial to unite Ago2 and RISC. TATA-binding protein-associated factor 11 assembles the RLC by facilitating Dcr-2-R2D2 tetramerization, which increases the binding affinity to siRNA by 10-fold.
Association with TAF11 would convert the R2-D2-Initiator complex into the RLC. R2D2 carries tandem double-stranded RNA-binding domains to recognize the thermodynamically stable terminus of siRNA duplexes, whereas Dicer-2 the other less stable extremity. Loading is asymmetric: the MID domain of Ago2 recognizes the thermodynamically stable end of the siRNA. Therefore, the "passenger" strand whose 5′ end is discarded by MID is ejected, while the saved "guide" strand cooperates with AGO to form the RISC. After integration into the RISC, siRNAs base-pair to their target mRNA and cleave it, thereby preventing it from being used as a translation template. Differently from siRNA, a miRNA-loaded RISC complex scans cytoplasmic mRNAs for potential complementarity. Instead of destructive cleavage, miRNAs rather target the 3′ untranslated region regions of mRNAs where they bind with imperfect complementarity, thus blocking the access of ribosomes for translation. Exogenous dsRNA is detected and bound by an effector protein, known as RDE-4 in C. elegans and R2D2 in Drosophila, that stimulates dicer activity.
The mechanism producing this length specifici
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen and nitrogen, although other elements are found in the side chains of certain amino acids. About 500 occurring amino acids are known and can be classified in many ways, they can be classified according to the core structural functional groups' locations as alpha-, beta-, gamma- or delta- amino acids. In the form of proteins, amino acid residues form the second-largest component of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first carbon atom have particular importance, they are known as α-amino acids. They include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins.
These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, in some antibiotics. Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids; the other two are selenocysteine, pyrrolysine. Pyrrolysine and selenocysteine are encoded via variant codons. N-formylmethionine is considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain and gamma-amino-butyric acid are the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells.
Carnitine is used in lipid transport. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for medical conditions. Essential amino acids may differ between species; because of their biological significance, amino acids are important in nutrition and are used in nutritional supplements, fertilizers and food technology. Industrial uses include the production of drugs, biodegradable plastics, chiral catalysts; the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus, subsequently named asparagine, the first amino acid to be discovered. Cystine was discovered in 1810, although its monomer, remained undiscovered until 1884. Glycine and leucine were discovered in 1820; the last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.
The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it. Usage of the term "amino acid" in the English language is from 1898, while the German term, Aminosäure, was used earlier. Proteins were found to yield amino acids after enzymatic acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide". In the structure shown at the top of the page, R represents a side chain specific to each amino acid; the carbon atom next to the carboxyl group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as alpha amino acids; these include amino acids such as proline which contain secondary amines, which used to be referred to as "imino acids". The alpha amino acids are the most common form found in nature, but only when occurring in the L-isomer.
The alpha carbon is a chiral carbon atom, with the exception of glycine which has two indistinguishable hydrogen atoms on the alpha carbon. Therefore, all alpha amino acids but glycine can exist in either of two enantiomers, called L or D amino acids, which are mirror images of each other. While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, D-amin
Ribonucleic acid is a polymeric molecule essential in various biological roles in coding, decoding and expression of genes. RNA and DNA are nucleic acids, along with lipids and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome; some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which RNA molecules direct the assembly of proteins on ribosomes; this process uses transfer RNA molecules to deliver amino acids to the ribosome, where ribosomal RNA links amino acids together to form proteins.
Like DNA, most biologically active RNAs, including mRNA, tRNA, rRNA, snRNAs, other non-coding RNAs, contain self-complementary sequences that allow parts of the RNA to fold and pair with itself to form double helices. Analysis of these RNAs has revealed that they are structured. Unlike DNA, their structures do not consist of long double helices, but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical catalysis. For instance, determination of the structure of the ribosome—an RNA-protein complex that catalyzes peptide bond formation—revealed that its active site is composed of RNA; each nucleotide in RNA contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, in general, cytosine, guanine, or uracil. Adenine and guanine are purines and uracil are pyrimidines. A phosphate group is attached to the 5' position of the next; the phosphate groups have a negative charge each. The bases form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil.
However, other interactions are possible, such as a group of adenine bases binding to each other in a bulge, or the GNRA tetraloop that has a guanine–adenine base-pair. An important structural component of RNA that distinguishes it from DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar; the presence of this functional group causes the helix to take the A-form geometry, although in single strand dinucleotide contexts, RNA can also adopt the B-form most observed in DNA. The A-form geometry results in a deep and narrow major groove and a shallow and wide minor groove. A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule, it can chemically attack the adjacent phosphodiester bond to cleave the backbone. RNA is transcribed with only four bases, but these bases and attached sugars can be modified in numerous ways as the RNAs mature. Pseudouridine, in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, ribothymidine are found in various places.
Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine. Inosine plays a key role in the wobble hypothesis of the genetic code. There are more than 100 other occurring modified nucleosides; the greatest structural diversity of modifications can be found in tRNA, while pseudouridine and nucleosides with 2'-O-methylribose present in rRNA are the most common. The specific roles of many of these modifications in RNA are not understood. However, it is notable that, in ribosomal RNA, many of the post-transcriptional modifications occur in functional regions, such as the peptidyl transferase center and the subunit interface, implying that they are important for normal function; the functional form of single-stranded RNA molecules, just like proteins requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements that are hydrogen bonds within the molecule; this leads to several recognizable "domains" of secondary structure like hairpin loops and internal loops.
Since RNA is charged, metal ions such as Mg2+ are needed to stabilise many secondary and tertiary structures. The occurring enantiomer of RNA is D-RNA composed of D-ribonucleotides. All chirality centers are located in the D-ribose. By the use of L-ribose or rather L-ribonucleotides, L-RNA can be synthesized. L-RNA is much more stable against degradation by RNase. Like other structured biopolymers such as proteins, one can define topology of a folded RNA molecule; this is done based on arrangement of intra-chain contacts within a folded RNA, termed as circuit topology. Synthesis of RNA is catalyzed by an enzyme—RNA polymerase—using DNA as a template, a process known as transcription. Initiation of transcription begins with the binding of the enzyme to a promoter sequence in the DNA; the DNA double helix is unwound by the helicase activity of the enzyme. The enzyme progresses along the template strand in the 3’ to 5’ direction, synthesizing a complementary RNA molecule with elongation occ