Banner
McCusker Oligonucleotide Therapeutics

McCusker Oligonucleotide Therapeutics

Research in our laboratory is focussed on developing novel nucleic acid-based technologies for therapeutic and diagnostic applications, mainly interested in tackling Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), Alzheimer’s disease and solid cancers.

 

We apply nucleic acid-based gene targeting principles, nucleic acid aptamers for target specific drug delivery, therapy and molecular imaging, nucleic acid-based nano-constructs for diagnosis and amplification etc.. 

 

Nucleic Acid Aptamers

Aptamers are short single-stranded DNA or RNA oligonuleotides that can bind to their target with very high affinity and specificity because of their ability to adopt 3D structures. They are normally selected from a randomised oligonucleotide pool by a reiterative process called SELEX (Systematic Evolution of Ligands by EXponential enrichment).

 

AptamerRef: Rakesh N. Veedu and Jesper Wengel, Mol Biosyst, 2009, 5, 787-792

 

Our ONE-STEP selection of Aptamers

In 2012, we have reported a rapid one-step selection methodology for developing nucleic acid aptamers. Please see the schematic illustration below.

 

ONE-STEP selection of AptamersRef: Lauridsen et al, PLoS ONE, 2012, 7, e41702

 

Stability of oligonucleotides

Oligonucleotides composed of naturally occurring nucleotides are rapidly degraded in vivo. This can be significantly improved by chemically-modified nucleic acid analogues. A number of nucleic acid analogues have been developed so far. One of the most prominent and successful analogue is called locked nucleic acid (LNA). In our research, we explore the applicability of LNA nucleotides to improve the binding affinity and nuclease resistance.

 

Stability of oligonucleotidesFor Reviews: 1. R. N. Veedu, J. Wengel*, RNA Biology, 2009, 6, 321 2. R. N. Veedu*, J. Wengel, Chemistry & Biodiversity, 2010, 7, 536

 

LNA Aptamers development

The remarkable properties of LNA nucleotides led us towards developing LNA-modified aptamers. However, in order to apply LNA nucleotides in SELEX processes for developing aptamers, LNA nucleotides must serve as substrates of DNA or RNA polymerases for enzymatic amplification and regeneration. Towards this goal, we have extensively studied and published various articles.

 

LNA Aptamers development[1]. Veedu RN, Vester B, Wengel J. J. Am. Chem. Soc., 2008, 130, 8124-8125 [2]. Veedu RN, Vester B, Wengel J. Chembiochem, 2007, 8, 490-492 [3]. Veedu RN, Wengel J. Mol. Biosyst, 2009, 5, 787-792 [4]. Wheeler W, et al. Chem Commun, 2012, 48, 11020-1102

 

Therapeutic LNA Aptamers

Against Breast Cancer: Recently, we have developed an LNA-modified DNA aptamer that can efficiently inhibit the breast cancer cell proliferation in vitro and in vivo. Currently, further validation are in progress.

 

Therapeutic LNA Aptamers

 

Alzheimer’s disease

We have also developed an LNA-modified DNA aptamer that can efficiently bind to low molecular weight soluble amyloid-beta peptide aggregates in confirmed Alzheimer brain hippocampus samples collected during autopsy.

Aptamer targeted Imaging

19F MRI against B16-melanoma: In 2013, my collaboration with Dr. Kristofer Thurecht at Center for Advanced Imaging, The University of Queensland demonstrated a highly sensitive aptamer conjugated hyperbranched polymeric nanosystem-based fluorine MRI detection system against B16 melanoma cells in mice.

 

Aptamer targeted Imaging

 

 

Rakesh N. Veedu, MSc, PhD MRACI

McCusker Fellow & Lead,
Center for Comparative Genomics &
Western Australian Neuroscience Research 
Institute, Murdoch University, Bld#390,
Discovery way, 90 South Street,
Murdoch, Perth, Western Australia 6150.
E-Mail : R.Veedu@murdoch.edu.au
Phone: +61 8 9360 6058

LATEST PUBLICATIONS See all
  • 24 July 2015

    The emperor's new dystrophin: finding sense in the noise

    READ MORE

  • 24 July 2015

    Editorial: medicinal chemistry of aptamers

    READ MORE