RNA Targeting Gene Therapy for Human Genetic Diseases

Adeno-associated virus (AAV) is a promising vector for in vivo gene therapy because of its excellent safety profile and ability to mediate stable gene expression in human subjects. However, there are still numerous challenges that need to be resolved before this gene delivery vehicle is used in clinical applications, such as the inability of AAV to effectively target specific tissues, preexisting neutralizing antibodies in human populations, and a limited AAV packaging capacity. Over the past two decades, much genetic modification work has been performed with the AAV capsid gene, resulting in a large number of variants with modified characteristics, rendering AAV a versatile vector for more efficient gene therapy applications for different genetic diseases.

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Artificial RNA Editing with ADAR for Gene Therapy

Current Gene Therapy ◽

10.2174/1566523220666200516170137 ◽

2020 ◽

Vol 20 (1) ◽

pp. 44-54 ◽

Cited By ~ 1

Author(s):

Sonali Bhakta ◽

Toshifumi Tsukahara

Keyword(s):

Gene Therapy ◽

Genetic Code ◽

Molecular Mechanism ◽

Rna Editing ◽

Comparative Studies ◽

Genetic Diseases ◽

Adenosine Deaminases ◽

Family Protein ◽

Hydrolytic Deamination

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.

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The Ocular Gene Delivery Landscape

Biomolecules ◽

10.3390/biom11081135 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1135

Author(s):

Bhubanananda Sahu ◽

Isha Chug ◽

Hemant Khanna

Keyword(s):

Gene Therapy ◽

Genetic Diseases ◽

Gene Therapies ◽

Advantages And Disadvantages ◽

Fda Approval ◽

New Information ◽

Efficient Delivery ◽

Delivery Routes ◽

History Of ◽

Different Parts

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

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RNA Editing as a Therapeutic Approach for Retinal Gene Therapy Requiring Long Coding Sequences

International Journal of Molecular Sciences ◽

10.3390/ijms21030777 ◽

2020 ◽

Vol 21 (3) ◽

pp. 777 ◽

Cited By ~ 6

Author(s):

Lewis E. Fry ◽

Caroline F. Peddle ◽

Alun R. Barnard ◽

Michelle E. McClements ◽

Robert E. MacLaren

Keyword(s):

Gene Therapy ◽

Rna Editing ◽

Therapeutic Approach ◽

Genetic Diseases ◽

Point Mutations ◽

Transcript Level ◽

Gene Replacement ◽

Promising Therapeutic Approach ◽

Pairing Site ◽

Large Genes

RNA editing aims to treat genetic disease through altering gene expression at the transcript level. Pairing site-directed RNA-targeting mechanisms with engineered deaminase enzymes allows for the programmable correction of G>A and T>C mutations in RNA. This offers a promising therapeutic approach for a range of genetic diseases. For inherited retinal degenerations caused by point mutations in large genes not amenable to single-adeno-associated viral (AAV) gene therapy such as USH2A and ABCA4, correcting RNA offers an alternative to gene replacement. Genome editing of RNA rather than DNA may offer an improved safety profile, due to the transient and potentially reversible nature of edits made to RNA. This review considers the current site-directing RNA editing systems, and the potential to translate these to the clinic for the treatment of inherited retinal degeneration.

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