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Nanobodies as novel agents for disease diagnosis and therapy.

Siontorou CG - Int J Nanomedicine (2013)

Bottom Line: The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging.Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities.This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes.

View Article: PubMed Central - PubMed

Affiliation: Department of Industrial Management and Technology, University of Piraeus, Piraeus, Greece.

ABSTRACT
The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging. Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities. This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes.

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Related in: MedlinePlus

The scientific roadmap of university-derived advancements in Camelidae HCAbs.Notes: Since their discovery in 1989, research groups moved fast to integrate Nbs in the well-established scientific frame of Ab-based biomedical tools. Although a clear distinction between the exploration and the exploitation phase cannot be made, and since even the latest papers are, to some extent, concerned with elucidation of mechanisms and physical chemistry, while the applicability domain was clearly defined in the introductory paper of 1993, a turning point can be found around 1998. As the spinoff, Ablynx, was moving to patenting and clinical testing at the early 2000s, the academic research groups were feeding a knowledge push mechanism until 2008, offering relations between properties and potential (until 2004), engineering trends (until 2006) and technology optimizations (until 2008). More researchers were attracted to join and extend the scientific network. Thereafter, the transition to a market pull mechanism becomes apparent, justifying Nbs as viable alternatives to Ab fragments, while a clear therapeutic advantage remains to be clinically proven. Superscripted numbers refer to published papers that document either a Nb asset or a stated intended use.Abbreviations: Ab, antibody; HC, heavy chain; Nb, nanobody; SPR, surface plasmon resonance; PEGylation, polyethylene glycol treatment; H, heavy; sd, single-domain; NMR, nuclear magnetic resonance; ER, endoplasmic reticulum.
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f2-ijn-8-4215: The scientific roadmap of university-derived advancements in Camelidae HCAbs.Notes: Since their discovery in 1989, research groups moved fast to integrate Nbs in the well-established scientific frame of Ab-based biomedical tools. Although a clear distinction between the exploration and the exploitation phase cannot be made, and since even the latest papers are, to some extent, concerned with elucidation of mechanisms and physical chemistry, while the applicability domain was clearly defined in the introductory paper of 1993, a turning point can be found around 1998. As the spinoff, Ablynx, was moving to patenting and clinical testing at the early 2000s, the academic research groups were feeding a knowledge push mechanism until 2008, offering relations between properties and potential (until 2004), engineering trends (until 2006) and technology optimizations (until 2008). More researchers were attracted to join and extend the scientific network. Thereafter, the transition to a market pull mechanism becomes apparent, justifying Nbs as viable alternatives to Ab fragments, while a clear therapeutic advantage remains to be clinically proven. Superscripted numbers refer to published papers that document either a Nb asset or a stated intended use.Abbreviations: Ab, antibody; HC, heavy chain; Nb, nanobody; SPR, surface plasmon resonance; PEGylation, polyethylene glycol treatment; H, heavy; sd, single-domain; NMR, nuclear magnetic resonance; ER, endoplasmic reticulum.

Mentions: Following the proof-of-concept, HCAbs have started to intrigue the scientific community as new Ab-based tools. In order to examine the dynamics of the research paths (ie, to determine technology boundaries and growth, and to decide on the incorporation of relevant terms and concepts that have been used interchangeably for nature-derived sdAbs, including Nb, sdAb, HCAb, single-chain Ab, and so on), the use of ontological data acquisition and mining tools has proven beneficial.16–18 The number of publications on Camelidae HCAbs and Nbs has risen dramatically since 2008, totaling up to 1,210 original articles in the Web of Science® database (Thomson Reuters, Philadelphia, PA, USA) published within 9 years (2004–2012) from 300 universities in 67 countries to cover the areas of molecular biology, immunology, hematology, and experimental medicine (Figure 1). The 10-year exploration phase, predominantly oriented to the elucidation of Nb structure and properties,13–15,19–24 was quickly followed by a rapidly increasing exploitation phase (Figure 2).25–58 This fast transition was enabled by the existing technological frame that offered an established research environment in terms of accumulated knowledge, capital outlays, infrastructure, and available skills. The scientific network, developed mostly by central European and US clusters, is field-specific and concrete, pushing and pulling players into finite sets of positions according to the needs for knowledge absorption. The number of possibilities and prospects with the technology at hand are numerous. This review outlines the current state of the art in Nbs, focusing on Nb structural features and properties, as well as its production and technology potential that also bears prospects for exploitation in other biotechnological fields.


Nanobodies as novel agents for disease diagnosis and therapy.

Siontorou CG - Int J Nanomedicine (2013)

The scientific roadmap of university-derived advancements in Camelidae HCAbs.Notes: Since their discovery in 1989, research groups moved fast to integrate Nbs in the well-established scientific frame of Ab-based biomedical tools. Although a clear distinction between the exploration and the exploitation phase cannot be made, and since even the latest papers are, to some extent, concerned with elucidation of mechanisms and physical chemistry, while the applicability domain was clearly defined in the introductory paper of 1993, a turning point can be found around 1998. As the spinoff, Ablynx, was moving to patenting and clinical testing at the early 2000s, the academic research groups were feeding a knowledge push mechanism until 2008, offering relations between properties and potential (until 2004), engineering trends (until 2006) and technology optimizations (until 2008). More researchers were attracted to join and extend the scientific network. Thereafter, the transition to a market pull mechanism becomes apparent, justifying Nbs as viable alternatives to Ab fragments, while a clear therapeutic advantage remains to be clinically proven. Superscripted numbers refer to published papers that document either a Nb asset or a stated intended use.Abbreviations: Ab, antibody; HC, heavy chain; Nb, nanobody; SPR, surface plasmon resonance; PEGylation, polyethylene glycol treatment; H, heavy; sd, single-domain; NMR, nuclear magnetic resonance; ER, endoplasmic reticulum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818023&req=5

f2-ijn-8-4215: The scientific roadmap of university-derived advancements in Camelidae HCAbs.Notes: Since their discovery in 1989, research groups moved fast to integrate Nbs in the well-established scientific frame of Ab-based biomedical tools. Although a clear distinction between the exploration and the exploitation phase cannot be made, and since even the latest papers are, to some extent, concerned with elucidation of mechanisms and physical chemistry, while the applicability domain was clearly defined in the introductory paper of 1993, a turning point can be found around 1998. As the spinoff, Ablynx, was moving to patenting and clinical testing at the early 2000s, the academic research groups were feeding a knowledge push mechanism until 2008, offering relations between properties and potential (until 2004), engineering trends (until 2006) and technology optimizations (until 2008). More researchers were attracted to join and extend the scientific network. Thereafter, the transition to a market pull mechanism becomes apparent, justifying Nbs as viable alternatives to Ab fragments, while a clear therapeutic advantage remains to be clinically proven. Superscripted numbers refer to published papers that document either a Nb asset or a stated intended use.Abbreviations: Ab, antibody; HC, heavy chain; Nb, nanobody; SPR, surface plasmon resonance; PEGylation, polyethylene glycol treatment; H, heavy; sd, single-domain; NMR, nuclear magnetic resonance; ER, endoplasmic reticulum.
Mentions: Following the proof-of-concept, HCAbs have started to intrigue the scientific community as new Ab-based tools. In order to examine the dynamics of the research paths (ie, to determine technology boundaries and growth, and to decide on the incorporation of relevant terms and concepts that have been used interchangeably for nature-derived sdAbs, including Nb, sdAb, HCAb, single-chain Ab, and so on), the use of ontological data acquisition and mining tools has proven beneficial.16–18 The number of publications on Camelidae HCAbs and Nbs has risen dramatically since 2008, totaling up to 1,210 original articles in the Web of Science® database (Thomson Reuters, Philadelphia, PA, USA) published within 9 years (2004–2012) from 300 universities in 67 countries to cover the areas of molecular biology, immunology, hematology, and experimental medicine (Figure 1). The 10-year exploration phase, predominantly oriented to the elucidation of Nb structure and properties,13–15,19–24 was quickly followed by a rapidly increasing exploitation phase (Figure 2).25–58 This fast transition was enabled by the existing technological frame that offered an established research environment in terms of accumulated knowledge, capital outlays, infrastructure, and available skills. The scientific network, developed mostly by central European and US clusters, is field-specific and concrete, pushing and pulling players into finite sets of positions according to the needs for knowledge absorption. The number of possibilities and prospects with the technology at hand are numerous. This review outlines the current state of the art in Nbs, focusing on Nb structural features and properties, as well as its production and technology potential that also bears prospects for exploitation in other biotechnological fields.

Bottom Line: The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging.Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities.This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes.

View Article: PubMed Central - PubMed

Affiliation: Department of Industrial Management and Technology, University of Piraeus, Piraeus, Greece.

ABSTRACT
The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging. Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities. This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes.

Show MeSH
Related in: MedlinePlus