Truncation and mutation of a transferrin receptor aptamer enhance binding affinity

Macdonald, Joanna, Houghton, Patrick, Xiang, Dongxi, Duan, Wei and Shigdar, Sarah 2016, Truncation and mutation of a transferrin receptor aptamer enhance binding affinity, Nucleic acid therapeutics, vol. 26, no. 6, pp. 348-354, doi: 10.1089/nat.2015.0585.

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Title Truncation and mutation of a transferrin receptor aptamer enhance binding affinity
Author(s) Macdonald, Joanna
Houghton, Patrick
Xiang, Dongxi
Duan, WeiORCID iD for Duan, Wei
Shigdar, SarahORCID iD for Shigdar, Sarah
Journal name Nucleic acid therapeutics
Volume number 26
Issue number 6
Start page 348
End page 354
Total pages 7
Publisher Mary Ann Liebert
Place of publication New Rochelle, N.Y.
Publication date 2016-12
ISSN 2159-3345
Summary Aptamers are proving their utility in a number of applications. However, to be easily functionalized, their structure needs to be simplified. Therefore, we sought to truncate a 50-nucleotide aptamer specific to the transferrin receptor to its smallest functional unit using rational engineering of the predicted two-dimensional structure of the longer parent sequence. In addition, mutations were introduced into the binding loop to determine their effect on the selectivity of the aptamers. These base mutations enhanced the binding affinity of the aptamer, while retaining its specificity. The equilibrium dissociation constant (Kd) was reduced sixfold following the substitution of all four bases in the binding region. In addition, these aptamers were efficiently internalized into transferrin receptor-positive cells in a similar manner to the transferrin receptor antibody and demonstrated colocalization with this antibody. This study has shown that the smallest functional unit of this aptamer was 14 nucleotides. This small size will be advantageous for future applications, such as drug delivery or functionalization of other therapeutic modalities.
Language eng
DOI 10.1089/nat.2015.0585
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Mary Ann Liebert
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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