Aptamer Technology: Adjunct Therapy for Malaria

Abstract

Malaria is a life-threatening parasitic infection occurring in the endemic areas, primarily in children under the age of five, pregnant women, and patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV)/(AIDS) as well as non-immune individuals. The cytoadherence of infected erythrocytes (IEs) to the host endothelial surface receptor is a known factor that contributes to the increased prevalence of severe malaria cases due to the accumulation of IEs, mainly in the brain and other vital organs. Therefore, further study is needed to discover a new potential anti-adhesive drug to treat severe malaria thus reducing its mortality rate. In this review, we discuss how the aptamer technology could be applied in the development of a new adjunct therapy for current malaria treatment.

Keywords: Plasmodium falciparum; adjunct therapy; aptamer; cytoadherence; malaria.

Figure 1

The effect of infected erythrocytes sequestration by various endothelial surface receptors and their disease phenotype. The diagram is modified from Penman et al. (2008) and Cabrera et al. (2014) [26,27].

Figure 2

The cytoadherence of infected erythrocytes to red blood cell and endothelial cell promotes the formation of rosetting, sequestration and platelet clumping. These infected erythrocytes (IEs) bind to a number of host receptors on the endothelial cell through tethering, rolling, and adhesion of IE on the surface. This cytoadherence of IEs to the host endothelial surface receptor prevents parasite clearance by the spleen. The diagram is modified from Rowe et al. (2009) [21].

Figure 3

RNA aptamer and DNA aptamer development. (A) Isolation of RNA aptamer targeting selected molecules requires an additional step to produce an RNA strand from single-stranded DNA through DNA transcription. Reverse transcription is needed to produce single-stranded DNA to produce an RNA pool for the subsequent SELEX cycle; (B) A separation step is required to produce single-stranded DNA from double-stranded DNA prior to the DNA aptamer selection. Commonly, the pool of aptamers begins with 10¹³ to 10¹⁴ random sequences which are then enriched into several groups of aptamers that specifically to their target. This can be achieved by sequencing the final bound product of SELEX and aligning the sequences. Further study is needed to measure the binding affinity of enriched aptamers to the target molecules.

Figure 3

RNA aptamer and DNA aptamer development. (A) Isolation of RNA aptamer targeting selected molecules requires an additional step to produce an RNA strand from single-stranded DNA through DNA transcription. Reverse transcription is needed to produce single-stranded DNA to produce an RNA pool for the subsequent SELEX cycle; (B) A separation step is required to produce single-stranded DNA from double-stranded DNA prior to the DNA aptamer selection. Commonly, the pool of aptamers begins with 10¹³ to 10¹⁴ random sequences which are then enriched into several groups of aptamers that specifically to their target. This can be achieved by sequencing the final bound product of SELEX and aligning the sequences. Further study is needed to measure the binding affinity of enriched aptamers to the target molecules.