molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and phys ...

, an intrabody (from ''

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

'' and ''

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...

'') is an antibody that works within the cell to bind to an intracellular

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

. Due to the lack of a reliable mechanism for bringing antibodies into a living cell from the extracellular environment, this typically requires the expression of the antibody within the target cell, which can be accomplished in transgenic animals or by

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human D ...

. As a result, intrabodies are defined as antibodies that have been modified for intracellular localization, and the term has rapidly come to be used even when antibodies are produced in

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...

s or other non-target cells. This term can apply to several types of protein targeting: the antibody may remain in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

, or it may have a

nuclear localization signal A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysine ...

, or it may undergo

cotranslational translocation :''This article deals with protein targeting in eukaryotes unless specified otherwise.'' Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the ce ...

across the membrane into the lumen of the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

, provided that it is retained in that compartment through a KDEL sequence. Because naturally occurring antibodies are optimised to be secreted from the cell, cytosolic intrabodies require special alterations, including the use of single-chain antibodies ( scFvs), modification of immunoglobulin VL domains for hyperstability, selection of antibodies resistant to the more reducing cytosolic environment, or expression as a fusion protein with maltose binding protein or other stable intracellular proteins. Such optimizations have improved the stability and structure of intrabodies, allowing the publication of a variety of promising applications against

hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. F ...

avian influenza Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.

prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...

diseases,

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

, and

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

. Optimizations required for cytosolic intrabodies are not needed for ER retained intrabodies, which fold in the compartment in which antibodies are naturally produced. Since the 1990s ER intrabodies have been used in various research areas to knock down membrane proteins and secreted proteins.

References

{{Engineered antibodies Antibodies