Research Topic

Oligonucleotide Therapeutics for Neurological Disorders and Injury: From Design to Delivery

About this Research Topic

Recently, we have witnessed the renaissance of the oligonucleotide therapeutics field as a whole, occurring on the shoulders of successful completion of a few clinical trials followed by the approval by medicinal product authorities. These recent success stories include
eteplirsen and nusinersen (Exondys 51/Spinraza, splice modulating oligonucleotides), Inotersen (TEGSEDI, gapmer antisense oligonucleotide) as well as patisiran (ONPATTRO, siRNA), the first ever approved RNAi drug.

These stories bode well for the foreseeable applications in the context of neurological disorders or injuries for which treatment options are limited and lack efficiency. With nusinersen already being a good example of an effective oligonucleotide drug for a neuromuscular disorder, it is expected that other neurological conditions will benefit from this oligo therapeutics momentum.

With the continuing advance of knowledge on the genetics and pathomechanisms of different neurological disorders and injury (e.g. Alzheimer, ALS, Parkinson, Huntington’s, stroke, traumatic brain injury, spinal cord injury), the potential for the application of oligonucleotide therapeutics (both single and double-stranded oligonucleotides) also expands. This potential is ever highlighted by the myriad of mechanisms employed by the different oligonucleotides which encompass not only the recently overviewed RNAi and RNAse H-based RNA degradation, but also steric blocking (be it at the RNA or even DNA level; e.g. splice modulating, miRNA inhibitors) and protein interacting (e.g. aptamers, CpG).
Of note is that, globally, it is expected that the burden of neurological disorders will continue to rise due to an increase in the world’s population and ageing thus continued advancements on the oligonucleotide therapeutics area for nervous system applications is warranted. In this regard, it will be important to address challenges such as delivery alternatives to the current intrathecal (IT) or intracerebroventricular (ICV) injections as methods to access the central nervous system, along with continued optimization of sequence selection, oligonucleotide design and biological activity in order to develop efficient oligonucleotide drugs while keeping an optimal safety profile.

This Research Topic aims to address the several areas involved in the development of oligonucleotide therapeutics focusing on nervous system applications ranging from current or novel modified nucleic acids chemistry and synthesis, oligonucleotide design, nervous system (targeted) delivery methods, as well as toxicological/immunological considerations. The Research Topic is open to both Original Research and Reviews.


Keywords: Nucleic Acid Chemistry, Drug Delivery, Nervous System, Neuronal Disorders, Therapeutic Oligonucleotides


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Recently, we have witnessed the renaissance of the oligonucleotide therapeutics field as a whole, occurring on the shoulders of successful completion of a few clinical trials followed by the approval by medicinal product authorities. These recent success stories include
eteplirsen and nusinersen (Exondys 51/Spinraza, splice modulating oligonucleotides), Inotersen (TEGSEDI, gapmer antisense oligonucleotide) as well as patisiran (ONPATTRO, siRNA), the first ever approved RNAi drug.

These stories bode well for the foreseeable applications in the context of neurological disorders or injuries for which treatment options are limited and lack efficiency. With nusinersen already being a good example of an effective oligonucleotide drug for a neuromuscular disorder, it is expected that other neurological conditions will benefit from this oligo therapeutics momentum.

With the continuing advance of knowledge on the genetics and pathomechanisms of different neurological disorders and injury (e.g. Alzheimer, ALS, Parkinson, Huntington’s, stroke, traumatic brain injury, spinal cord injury), the potential for the application of oligonucleotide therapeutics (both single and double-stranded oligonucleotides) also expands. This potential is ever highlighted by the myriad of mechanisms employed by the different oligonucleotides which encompass not only the recently overviewed RNAi and RNAse H-based RNA degradation, but also steric blocking (be it at the RNA or even DNA level; e.g. splice modulating, miRNA inhibitors) and protein interacting (e.g. aptamers, CpG).
Of note is that, globally, it is expected that the burden of neurological disorders will continue to rise due to an increase in the world’s population and ageing thus continued advancements on the oligonucleotide therapeutics area for nervous system applications is warranted. In this regard, it will be important to address challenges such as delivery alternatives to the current intrathecal (IT) or intracerebroventricular (ICV) injections as methods to access the central nervous system, along with continued optimization of sequence selection, oligonucleotide design and biological activity in order to develop efficient oligonucleotide drugs while keeping an optimal safety profile.

This Research Topic aims to address the several areas involved in the development of oligonucleotide therapeutics focusing on nervous system applications ranging from current or novel modified nucleic acids chemistry and synthesis, oligonucleotide design, nervous system (targeted) delivery methods, as well as toxicological/immunological considerations. The Research Topic is open to both Original Research and Reviews.


Keywords: Nucleic Acid Chemistry, Drug Delivery, Nervous System, Neuronal Disorders, Therapeutic Oligonucleotides


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

21 August 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

21 August 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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