The below terms are defined in the context of aptamers and antibodies.
Aptamer - Synthetically created nucleic acid oligomer, usually 40-60 nucleotides in
length, that binds to specific targets with high affinity and specificity - they essentially act
as synthetic antibodies with a wider range of possible targets. Coined by Andrew Ellington,
the word is derived from "aptus" - Latin for "fit," and "mers" - Greek for "part."
Affinity - The strength of the bond between ligand and target.
Specificity - The accuracy in which a ligand determines its target.
Disease - Condition that impairs normal function in a living plant or animal.
Oligonucleotide - A nucleic acid structure that contains a relatively small
amount of nucleotide - to establish context, organism DNA usually contains thousands
of nucleotides. Derived from "oligo" - Greek.
SELEX - [Sel - leks ] - Systematic Evolution of Ligands by Exponential Enrichment, a synthetic process in which aptamers are isolated based on having desirable qualities.
Therapeutic - Relating to the treatment of diseases or disorders.
Diagnostic - Relating to the diagnosis of a disease or disorder.
Ligand - A molecule, such as an antibody, hormone, drug, or aptamer that binds to a larger, central molecule.
Aptamer-Target Complex - Refers to the combined molecular
body when the aptamer is bound to the molecular target, together forming a
larger molecule - the aptamer is acting as a ligand.
Peptide - Natural and synthetic compound containing two or more amino
acids.
DNA - Deoxyribonucleic acid, a nucleic acid composed of the four nucleotides adenine, guanine, cytosine, and thymine - typically exists as a double stranded double helix. DNA aptamers are single stranded and called ssDNA.
RNA - Ribonucleic acid, a nucleic acid that is single-stranded and contains the same four nucleotides of DNA, except with uracil replacing thymine. RNA is transcribed from DNA and typically used naturally to carry genetic information, such as for protein synthesis. RNA aptamers display slightly different properties then DNA aptamers.
Transcription - Process in which RNA is synthesized from DNA - complementary base pairs (cytosine to guanine, and thymine to adenine) are matched to create an opposite RNA strand. Thymine is substituted for uracil. This synthesized RNA is then used to transport genetic information, typically for protein synthesis or replication of the genetic information.
Pharmacokinetics - Process by which a drug is absorbed, distributed, metabolized, and eliminated by the body, or the study of this process.
In vitro - Latin: "in glass," artificial environment outside a living organism - commonly called a "test tube environment."
In vivo - Latin: "in a living thing," occurring inside a living organism, in the context of pharmacokinetics, refers to the conditions a therapeutic drug is subject to.
kDa - kDa stands for kilo-dalton, a non-SI (International System of Units) atomic and molecular mass unit and is approximately equal to 1.660538782(83)×10 kg.
Conjugation - Joining; a union.
PCR - Polymerase Chain Reaction, a process that amplifies DNA, capable of making thousands or millions of copies in a short period of time of even DNA segments.
Assay - An analysis or examination, diagnostic assays are simply analyzing tests.
(Text Citation 3, Text Citation 5, Text Citation 55, Text Citation 56, Text Citation 59)
Oligo: ολιγο
Aptamers:
Below is an overview of this website, intended for a more streamlined overall educational experience of this topic. Information is presented in order, along with important background and context.
Using this page, you will be armed with the knowledge to jump right into the world of aptamers.
An Overview
Terms To Know
Directory A Guide to Site Content
- Lists and describes the three types of aptamers, their structures, how they recognize and bind to their targets, and how they treat disease.
- History of development of the "magic bullet" concept, as realized in Monoclonal Antibodies (mAbs), and culminating in aptamers. Details the development of the SELEX process and clinical drug development.
- Description of how aptamers are generated in the SELEX process.
- How aptamers are used to therapeutically - how they treat disease. Includes highlighted sections on Age-Related Macular Degeneration (AMD) and Human Immunodeficiency Virus (HIV).
- Social and economic impacts of aptamers, controversies associated with aptamers, and comparison versus Monoclonal Antibodies. Comparison page also lists aptamer properties.
- Scientists and companies that are leaders in aptamer development.
- All sources cited here. Contact information also included.
Aptamer bound to a target protein, forming an Aptamer-Target Complex
Aptamer bound to a target protein, forming an Aptamer-Target Complex
The drug development process lives in some degree of infamy for its arduousness. Understanding this process is key to understanding why every advance in therapeutic drugs, in saving time and money or improving efficiency, is significant. This process is summarized in the above video (Video Citation 13). Click below for a more in depth summary of this process. All drugs (including aptamer-based drugs) must undergo this process to receive FDA approval to be distributed for use.
Page Content
• Aptamer Advantages
• Site Directory
• Terms to Know
• Drug Development Overview
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and can be selected through SELEX in hours, and are isolated, rather then created - aptamers already exist; they just have to be found.
Production: Aptamer production can be carried out completely in vitro, or in test tubes, environmental conditions can be custom-determined, as they are not subject to an animal's. This process is also quicker and cheaper then the expensive cell lines of mAbs.
Targets: Aptamers have a virtually unlimited spectrum of targets, including molecules antibodies do not recognize.
Immunogenicity: Because nucleic acid is not recognized by the immune system as foreign, aptamers have low risk for an undesirable immune response against them, which would be a powerful side effect and detriment to aptamer-based drugs (mAbs sometimes induce immune responses).
Size: Because of their small size, aptamers, even when conjugated, can traverse the body in ways larger molecules, such as antibodies, cannot - such as accessing small areas. Circumstances in which small size is a disadvantage can be remedied by conjugation (See Below).
Ability to be Modified: Aptamers can be readily modified, whether by chemically altering their structures, or attachment, or conjugation, of additional parts such as polyethylene glycol (PEG) to resist renal filtration, or to drugs (i.e. chemotherapy drug doxorubicin), toxins, and siRNAs.
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Aptamer Advantages
Stability: Aptamers can withstand cycles of denaturation/renaturation, retaining their structures - antibodies are easily irreversibly denatured. Aptamers are also resistant to high temperatures, and have an unlimited shelf life and do not require refrigeration.
Selection/Discovery: Aptamers are the product of a series of evolutionary chemical processes
The Drug Development Process
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Background Resources
Additional background pages are displayed here - they are also linked on the pages of the issue to which they pertain.