by Nanobodies, also known as single domain antibodies, are antibody fragments derived from camelid species such as camel, llama and alpaca. They consist of a single variable domain found in heavy chain antibodies unique to camelids. Unlike conventional antibodies which have a Y-shaped structure consisting of two heavy and two light chains, nanobodies have only a single domain which retains the antigen binding site.
Nanobodies were first discovered in 1989 by researchers at the Vrije Universiteit Brussel in Belgium. Since then, their unique characteristics such as small size, stability, solubility and ease of production have made nanobodies attractive alternatives to conventional monoclonal antibodies. In recent years, the United States has actively explored potential applications of nanobodies in biomedical research and therapy.
Growing Applications In Research And United States Nanobodies
Due to their small size of only 12-15 kDa, nanobodies can access binding sites on antigens that are cryptic or inaccessible to conventional antibodies. This has enabled applications in molecular imaging, intracellular labeling and therapeutic delivery. For instance, nanobodies were successfully used to image amyloid plaque deposition in the brains of Alzheimer’s disease models.
Nanobodies’ stability allows them to withstand harsh conditions like heat, acids and lytic enzymes, making them suitable tools for medical diagnostics. Their high affinity and specificity also allow accurate detection of biomarkers. For example, a nanobody-based rapid test was developed by the National Institutes of Health to detect SARS-CoV-2 nucleocapsid protein in patient samples.
Therapeutic Applications Hold Promise
Given nanobodies’ ability to penetrate tissues and access intracellular targets, they hold promise as novel biotherapeutics. Nanobodies can serve as antiviral and anticancer therapies by neutralizing pathogens or blocking oncogenic protein interactions. Preclinical studies showed nanobodies were effective against respiratory syncytial virus, Ebola virus and SARS-CoV-2.
Camelid nanobodies against tumor necrosis factor alpha successfully progressed to clinical trials for treatment of inflammatory conditions like rheumatoid arthritis with positive outcomes. This validated nanobodies as a therapeutic platform and spurred companies like Ablynx, MorphoSys and Merck to advance other nanobody candidates into clinical testing against cancer and viral diseases.
Government Funding Drives Research Momentum
Acknowledging nanobodies’ potential, the United States government has boosted funding for nanobody research through agencies like NIH and DARPA. In 2019, NIH awarded $4.5 million to establish three Camellid Nanobody Cores located at research institutes including The Scripps Research Institute. These cores work to generate and characterize nanobody libraries against diverse targets to serve the research community.
DARPA supported multiple projects under its Preventing Emerging Pathogenic Threats program to develop nanobody-based therapies against potential pandemics. Companies such as Camelid Therapeutics and Anthropic received millions in funding from DARPA to advance nanobody programs against influenza, coronaviruses and other priority pathogens. Such sustained government support has helped strengthen the United States’ leadership in nanobody research.
Outlook – Overcoming Challenges
While nanobodies hold great potential, some challenges remain. Their small size can lead to rapid clearance by the kidneys, limiting dosing frequency. However, approaches like PEGylation, fusion to albumin-binding domains or nanoparticle formulation can extend plasma half-life to therapeutic levels. Immunogenicity is another challenge but humanization of nanobodies may help mitigate immune responses.
With continued investments and inter-institutional collaborations, the United States is well-positioned to translate nanobody discoveries into novel diagnostics and therapies. Leveraging organizations like the three new Camellid Nanobody Cores, research momentum is expected to grow. If challenges in manufacturability and half-life extension can be overcome, nanobodies may revolutionize biomedicine in the coming decades.
About Author - Alice Mutum
Alice Mutum is a seasoned senior content editor at Coherent Market Insights, leveraging extensive expertise gained from her previous role as a content writer. With seven years in content development, Alice masterfully employs SEO best practices and cutting-edge digital marketing strategies to craft high-ranking, impactful content. As an editor, she meticulously ensures flawless grammar and punctuation, precise data accuracy, and perfect alignment with audience needs in every research report. Alice's dedication to excellence and her strategic approach to content make her an invaluable asset in the world of market insights. LinkedIn
