In vivo SELEX for Identification of Brain-penetrating Aptamers

Cheng, Congsheng; Chen, Yong Hong; Lennox, Kim A.; Behlke, Mark A.; Davidson, Beverly L.

doi:10.1038/mtna.2012.59

Cited by 171 publications

(172 citation statements)

References 42 publications

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“…The blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSFB) consists of a set of physiological mechanisms that protect the brain from infectious and toxic agents and also impedes drug transport. The BBB is composed of brain capillary endothelial cells, pericytes, astrocytic foot processes, and nerve endings terminating on the capillary surface [16]. The BCSFB is composed of choroid plexus epithelial cells [17].…”

Section: Introductionmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

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Section: Introductionmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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“…With the basic developments in SELEX, different strategies have been demonstrated for generating cell-internalizing aptamers, such as whole-cell SELEX (also termed cellinternalization SELEX or cell-SELEX) and in vivo SELEX (Mi et al 2010;Thiel et al 2012;Zhou et al 2012;Cheng et al 2013;Gourronc et al 2013;Camorani et al 2014;Yan 2014). These SELEX processes target membrane/surfacebound antigens, leading to the production of internalizing aptamers.…”

Section: Cell-targeted Aptamer Generation-selex Methodsmentioning

confidence: 99%

“…Although internalizing aptamers can be generated by whole cell-SELEX, as stated above, they can also be generated via tissue penetration using the SELEX strategies demonstrated by Mi et al (2010) and Cheng et al (2013). Mi et al (2010) generated an aptamer to target tumors based on in vivo SELEX.…”

Section: Tissue-specific Selexmentioning

confidence: 99%

“…The targeted tissue will be dissected for isolation of bound molecules. Three mandatory steps are complex formation, partition, and amplification Similarly, Cheng et al (2013) used a 2′fluoropyrimidine-modified RNA library and made injections into the tail vein of a mouse, after which molecules bound to the brain tissue were extracted and amplified to proceed with the next round of SELEX. Overall, 90 % of the sequences had three motifs that were found after 22 rounds of SELEX.…”

Section: Tissue-specific Selexmentioning

confidence: 99%

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Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath

Lakshmipriya

Chen

et al. 2016

Appl Microbiol Biotechnol

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Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

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“…Aptamers are defined as small sequence of nucleotides which are engineered through repeated rounds of in vitro systematic evolution of ligands by exponential enrichment (SELEX) and can sense specific molecular targets with high selectivity [1][2][3][4]. RNA aptamers are characterized by unpaired or mismatched bases which help to fold the RNA in distinct secondary and tertiary structures containing loops and bulges.…”

Section: Introductionmentioning

confidence: 99%