Rare Monogenic Diseases: Molecular Mechanism and Novel Therapies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 15 September 2024 | Viewed by 4842

Special Issue Editors


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Guest Editor
College of Medical Sciences, University of Rzeszów, 35-315 Rzeszów, Poland
Interests: clinical genetics; paediatrics, neonatology; rare diseases; monogenic diseases; chromosome disorders

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Guest Editor
Department of Clinical Genetics, College of Medical Sciences, University of Rzeszów, 35-959 Rzeszów, Poland
Interests: clinical genetics; genetic counselling; inborn errors of metabolism; neonatology; paediatrics; neurological and psychiatric diseases; epigenetics

E-Mail Website
Guest Editor
College of Medical Sciences, University of Rzeszów, 35-315 Rzeszów, Poland
Interests: paediatric endocrinology; paediatric diabetology; obesity, metabolic syndrome; diabetes; insulin resistance

Special Issue Information

Dear Colleagues,

Over the past decades, the development of molecular biology and research into exploring the human genome has contributed to understanding the molecular mechanisms underlying the pathology in rare monogenic diseases. This has led to attempts to use therapies based on correcting or bypassing the molecular problem, including replacement therapies or gene therapy.

Gene therapy traces its origins to the early 1990s. Numerous clinical trials have been conducted in various disease entities, using different vectors and mechanisms to deliver the correct gene to target cells. However, the molecular basis of many diseases is not yet fully understood, and therapy attempts are limited to laboratory models and preclinical studies. There is a great need to supplement this knowledge and develop new therapies that can be successfully applied to humans.

For this Special Issue, we invite molecular and cell biology experts, medical and clinical geneticists, paediatricians, chemists and other professionals who carry out research in molecular mechanisms, cell biology, nanoparticles, vectors, gene delivery systems, genome editing systems, clinical trials and other aspects of novel therapies for rare monogenic diseases.

Dr. Paweł Zapolnik
Dr. Antoni Pyrkosz
Prof. Dr. Artur Mazur
Guest Editors

Manuscript Submission Information

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Keywords

  • rare diseases
  • monogenic diseases
  • genetics
  • molecular biology
  • molecular pathways
  • gene therapy
  • gene delivery
  • molecular medicine

Published Papers (2 papers)

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Research

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16 pages, 5081 KiB  
Article
Successful Correction by Prime Editing of a Mutation in the RYR1 Gene Responsible for a Myopathy
by Kelly Godbout, Joël Rousseau and Jacques P. Tremblay
Cells 2024, 13(1), 31; https://doi.org/10.3390/cells13010031 - 22 Dec 2023
Cited by 1 | Viewed by 3169
Abstract
We report the first correction from prime editing a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The [...] Read more.
We report the first correction from prime editing a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which leads to motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows for the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the prime editing components. It is to be noted that T4709M is recessive and, thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that correcting mutations in the RYR1 gene is possible. Full article
(This article belongs to the Special Issue Rare Monogenic Diseases: Molecular Mechanism and Novel Therapies)
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Review

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14 pages, 2456 KiB  
Review
Chromosome Transplantation: Opportunities and Limitations
by Angela La Grua, Ilaria Rao, Lucia Susani, Franco Lucchini, Elena Raimondi, Paolo Vezzoni and Marianna Paulis
Cells 2024, 13(8), 666; https://doi.org/10.3390/cells13080666 - 11 Apr 2024
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Abstract
There are thousands of rare genetic diseases that could be treated with classical gene therapy strategies such as the addition of the defective gene via viral or non-viral delivery or by direct gene editing. However, several genetic defects are too complex for these [...] Read more.
There are thousands of rare genetic diseases that could be treated with classical gene therapy strategies such as the addition of the defective gene via viral or non-viral delivery or by direct gene editing. However, several genetic defects are too complex for these approaches. These “genomic mutations” include aneuploidies, intra and inter chromosomal rearrangements, large deletions, or inversion and copy number variations. Chromosome transplantation (CT) refers to the precise substitution of an endogenous chromosome with an exogenous one. By the addition of an exogenous chromosome and the concomitant elimination of the endogenous one, every genetic defect, irrespective of its nature, could be resolved. In the current review, we analyze the state of the art of this technique and discuss its possible application to human pathology. CT might not be limited to the treatment of human diseases. By working on sex chromosomes, we showed that female cells can be obtained from male cells, since chromosome-transplanted cells can lose either sex chromosome, giving rise to 46,XY or 46,XX diploid cells, a modification that could be exploited to obtain female gametes from male cells. Moreover, CT could be used in veterinary biology, since entire chromosomes containing an advantageous locus could be transferred to animals of zootechnical interest without altering their specific genetic background and the need for long and complex interbreeding. CT could also be useful to rescue extinct species if only male cells were available. Finally, the generation of “synthetic” cells could be achieved by repeated CT into a recipient cell. CT is an additional tool for genetic modification of mammalian cells. Full article
(This article belongs to the Special Issue Rare Monogenic Diseases: Molecular Mechanism and Novel Therapies)
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