Highly efficient inhibition of human immunodeficiency virus type 1 reverse transcriptase by aptamers functionalized gold nanoparticles

Abstract

We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45-Au NPs shows inhibitory efficiency in the retroviral replication cycle with a decreasing infectivity (40.2%).

ChemInform Abstract: Biomedical Applications of DNA‐Conjugated Gold Nanoparticles

“…Schematic representation of the binding and enzymaticactivity of HIV-1 RT toward poly(rA):oligo(dT)12-18 A) in the absence and B) in the presence of aptamer-AuNPs. [136] ChemBioChem 2016, 17,1052 -1062 www.chembiochem.org…”

“…[135] Shiang et al showedt hat these two aptamers-conjugated AuNPs (each 13 nm in diameter) are highly effective inhibitors for HIV-1 RT, with their designp rincipless hown in Figure 8. [136] They found that the loading density of aptamersa nd the linker length between the aptamer and AuNPs both play important roles in determining their inhibition activity.W hen 40 ODN 93 aptamers were conjugated onto the surface of AuNP with aT 45 linker length,t he aptamer-AuNPc omplexes showedi nhibitory efficiency in the retroviral replication cycle, with ar educed infectivity of 40.2 %.…”

Gold Nanoparticles to Improve HIV Drug Delivery

“…Very few approaches using AuNPs as carrier for anti-HIV drugs have been reported [30,31]. Our groups tested in a previous work that AuNPs conjugated to a CCR5 antagonist, reduced viral production [13].…”

Predicting Future Prospects of Aptamers in Field-Effect Transistor Biosensors

“…Meanwhile, aptamers that can select various proteins of HIV type 1 (HIV-1) including Rev protein [43,44], reverse transcriptase (RT) [43,45], and Tat [43] were recognized for their potential in therapeutics. Many of them have been continuously developed to inhibit the RT protein of HIV [46][47][48][49][50][51][52]. In a battle to replace antibodies destroyed by the virus, the spotlight gradually shifted to the diagnostic and therapeutic functions of aptamers in targeting immune systems [53,54].…”