Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology
Abstract The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of ther...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02356-y |
| _version_ | 1797863461205573632 |
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| author | Derek Hong Lilia M. Iakoucheva |
| author_facet | Derek Hong Lilia M. Iakoucheva |
| author_sort | Derek Hong |
| collection | DOAJ |
| description | Abstract The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of therapeutics for ASD. Given the role of LoF mutations in ASD etiology, many of the therapeutics in development are designed to rescue the haploinsufficient effect of genes at the transcriptional, translational, and protein levels. This review will discuss the various therapeutic techniques being developed from each level of the central dogma with examples including: CRISPR activation (CRISPRa) and gene replacement at the DNA level, antisense oligonucleotides (ASOs) at the mRNA level, and small-molecule drugs at the protein level, followed by a review of current delivery methods for these therapeutics. Since central nervous system (CNS) penetrance is of utmost importance for ASD therapeutics, it is especially necessary to evaluate delivery methods that have higher efficiency in crossing the blood-brain barrier (BBB). |
| first_indexed | 2024-04-09T22:35:57Z |
| format | Article |
| id | doaj.art-5842c94de0bf4186b1b6e00e7f1f3149 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-09T22:35:57Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-5842c94de0bf4186b1b6e00e7f1f31492023-03-22T12:27:30ZengNature Publishing GroupTranslational Psychiatry2158-31882023-02-0113111410.1038/s41398-023-02356-yTherapeutic strategies for autism: targeting three levels of the central dogma of molecular biologyDerek Hong0Lilia M. Iakoucheva1Department of Psychiatry, University of California San DiegoDepartment of Psychiatry, University of California San DiegoAbstract The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of therapeutics for ASD. Given the role of LoF mutations in ASD etiology, many of the therapeutics in development are designed to rescue the haploinsufficient effect of genes at the transcriptional, translational, and protein levels. This review will discuss the various therapeutic techniques being developed from each level of the central dogma with examples including: CRISPR activation (CRISPRa) and gene replacement at the DNA level, antisense oligonucleotides (ASOs) at the mRNA level, and small-molecule drugs at the protein level, followed by a review of current delivery methods for these therapeutics. Since central nervous system (CNS) penetrance is of utmost importance for ASD therapeutics, it is especially necessary to evaluate delivery methods that have higher efficiency in crossing the blood-brain barrier (BBB).https://doi.org/10.1038/s41398-023-02356-y |
| spellingShingle | Derek Hong Lilia M. Iakoucheva Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology Translational Psychiatry |
| title | Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology |
| title_full | Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology |
| title_fullStr | Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology |
| title_full_unstemmed | Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology |
| title_short | Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology |
| title_sort | therapeutic strategies for autism targeting three levels of the central dogma of molecular biology |
| url | https://doi.org/10.1038/s41398-023-02356-y |
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