40 Years of Studying RNA Import into Mitochondria: From Basic Mechanisms to Gene Therapy Strategies

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

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Gene therapy strategies for idiopathic pulmonary fibrosis: recent advances, current challenges, and future directions

Molecular Therapy — Methods & Clinical Development ◽

10.1016/j.omtm.2021.01.003 ◽

2021 ◽

Vol 20 ◽

pp. 483-496

Author(s):

Mitchel J.R. Ruigrok ◽

Henderik W. Frijlink ◽

Barbro N. Melgert ◽

Peter Olinga ◽

Wouter L.J. Hinrichs

Keyword(s):

Gene Therapy ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Future Directions ◽

Recent Advances ◽

Therapy Strategies

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Regulatory considerations for gene-therapy strategies and products

Trends in Biotechnology ◽

10.1016/0167-7799(93)90112-m ◽

1993 ◽

Vol 11 (5) ◽

pp. 189-191 ◽

Cited By ~ 5

Author(s):

Nelson A. Wivel

Keyword(s):

Gene Therapy ◽

Therapy Strategies

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Potential HIV gene therapy strategies

10.31219/osf.io/e5hm2 ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Gene Therapy ◽

Cord Blood ◽

Gene Editing ◽

Mortality Risks ◽

Recent Advances ◽

Whole Exome ◽

Localization Signal ◽

Cord Blood Cells ◽

The Cost ◽

Therapy Strategies

The CCR5 null genotype generation has been a main focus in the HIV gene therapy industry. The presence of the X4 tropic virus, mobilization of HSPCs, the quality of the cells for manipulation, and gene editing efficiency appear to be the main obstacles in translating this technique. Unintended off-target cleavage is a key problem in CRISPR/Cas9 editing. With the development of small molecule expansion methods for cord blood HSPC, it would be advantageous to modify CCR5 in cord blood cells and expand them for transplantation. The generation of engraftable HSPCS from iPSCs would be an ideal technique for HSCC gene therapy.The haplotype-characterized iPSC would be the donor for many patients, and it could be a commercially available product. The 32 C CR5 homozygous people had no elevated mortality risks according to whole-exome sequencing and whole-genome genotyping, according to CCR 5 positive people, and had no higher mortality risks compared to those who were HIV positive. Recent advances in gene editing, such as non-viral delivery of Cas9 ribonucleoproteins, incorporation of a 3X-nuclear localization signal into spCas9, and use of HiFi Cas9 with chemically modified sgRNAs, can be combined with recent advances in transplantation. Infusing modest doses of gene modified primitive HSPC fractions indicated by CD34 + CD90 + CD45RA-, which can engraft better, is another option for lowering the cost of gene therapy.

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