As targeted therapies evolve and the limitations of antibody-based therapies become clearer, a growing number of research teams are exploring the therapeutic potential of aptamers.

Aptamer Treatment for Dementia

Autoimmunity and autoantibodies have been implicated in the pathogenesis of a growing number of disorders. A research team in Germany recently confirmed the presence of functional autoantibodies against G-protein coupled receptors in serum from patients with Alzheimer’s and vascular dementia. Based on binding and epitope-mapping studies, aptamer BC007 with selectivity for the GPCR-AAB FAB fragment was developed as a “broad spectrum neutralizer”.  When tested in a bioassay consisting of spontaneously beating cultured neonatal rat cardiomyocytes, aptamer BC007 completely neutralized function of the GPCR-AABs. Successful in vitro neutralization suggests potential utility of the BC007 aptamer as an in vivo treatment for dementia patients (2).

Aptamers for Protection Against Acute Stroke

Toll-like receptor 4 (TLR4) is a key player in the adaptive immune response. It is involved in several pathologies including stroke, myocardial infarction, atherosclerosis, sepsis, multiple sclerosis, and chronic pain. Researchers in Spain have investigated TLR4-blocking DNA aptamers specifically for stroke treatment. The selected aptamer inhibited activity in both LPS-stimulated HEK-blue-hTLR4 cells and peritoneal macrophages stimulated with LPS. In in vivo studies involving mice and rats subjected to permanent middle cerebral artery occlusion (pMCAO), the TLR4-blocking aptamer reduced ischemic brain injury when administered 4 or 6 hours after injury, the typical time frame for administration of stroke treatment. Imaging studies showed aptamer presence in the blood and in the brain. Continued protective effects were observed at the final 21-day time point. While stroke treatment with tissue plasminogen activator, tPA, is a valid option in only 5% of cases, TLR4-blocking aptamers are a promising, non-toxic alternative (1).   

Aptamer Treatment for Parkinson’s

The aggregation of α-synuclein protein in neurons has been implicated in the pathogenesis of Parkinson’s Disease. While anti-α-synuclein antibody treatment has shown some success, antibody-based immunotherapy is limited by the inherent immunogenicity of antibodies and the inability of antibodies to access intracellular targets. Aptamer-based immunotherapy is an attractive alternative. Researchers in China have reported preliminary results for a selective aptamer to α-synuclein. In vitro, the aptamer inhibited α-synuclein aggregation and association with mitochondria. It also promoted intracellular α-synuclein degradation and preserved neuron viability in the presence of α-synuclein over-expression. In vivo, the α-synuclein aptamer could potentially prevent α-synuclein aggregation, promote the clearance of existing aggregates, and reduce toxic effects of α-synuclein aggregates on neurons (3).

Aptamer Therapeutic for Multiple Myeloma

Multiple myeloma (MM) is a malignant cancer affecting bone marrow that is associated with over-expression of the Annexin A2 protein (ANXA2). ANXA2 is believed to be involved with both MM adhesion and growth. Researchers in China have developed an aptamer selective for the ANXA2 protein in both mouse samples and clinical MM patient samples. The aptamer blocked adhesion of MM.1.S cells and RPMI-8226 cells to ANXA2 and prevented ANXA2-induced proliferation, suggesting potential utility for therapeutic treatment (4).

Aptamer Advantages in Therapeutics

Antibody specificity and affinity have enabled the development of a wide range of diagnostic tests and therapeutic agents. Aptamers offer similar specificity and affinity to antibodies with several added advantages. Promising in vitro tests and in vivo animal studies, coupled with the many aptamer advantages, have paved the way for human trials and exciting new aptamer-based therapies.

Chemical Synthesis: Because aptamers are chemically synthesized, there is an unlimited supply of aptamer with high batch-to-batch consistency. Chemical synthesis eliminates concerns over cell culture-derived contaminants associated with bioprocessing and simplifies the regulatory process.

Simple Modification: Aptamers are easily conjugated for in vitro and in vivo detection or complexing with other molecules for cell targeting or assisted penetration of the blood-brain barrier without loss of function.

Small Size: Small aptamer size helps facilitate entry into tissues and cells (1,2,3). Some aptamers, including the TLR4 aptamer above, have penetrated the blood-brain barrier, enabling better treatment of neurological disorders.

No Immunogenicity: Aptamers are generally non-immunogenic. In toxicity studies, the TLR4 aptamer showed no toxic effects on tissues or organs (1). Reduced immunogenicity/toxicity enables higher doses of drug and improved drug performance with fewer side effects.

Stability: Aptamers are also more thermally stable, which is important for storage and transport in a wide range of geographic areas (1,2,3).

In Vitro Aptamer Discovery: Aptamer development is an in vitro process which can be much faster and more cost effective than antibody production.  

Selection of Therapeutic Aptamers

Base Pair has years of experience performing multiplex selection of aptamers to a wide range of targets, including circulating proteins, cell surface markers, and small molecules. Selecting aptamers to several related targets and incorporating modifications for enhanced in vivo stability in a single project can increase chances of success and reduce time to market with new therapeutics.

Contact Base Pair today to learn more about aptamer development for therapeutics.


  1. Fernandez, G. et al. TLR4-binding DNA aptamers show a protective effect against acute stroke in animal models. Molecular Therapy. 2018.
  2. Walukat, G., et al. Functional autoantibodies in patients with different forms of dementia. PLoS One. 2018. 13(3):e0192778.
  3. Zheng, Y., et al. Novel DNA aptamers for parkinson’s disease treatment inhibit a-synuclein aggregation and facilitate its degradation. Molecular Therapy Nucleic Acids. 2018. 11:228-242.
  4. Zhou, W., et al. Screening and characterization of an Annexin A2 binding aptamer that inhibits the proliferation of myeloma cells. Biochimie. 2018. 151:150-158.