Gene Therapy for the COL7A1 Gene

Mayr, Elisabeth; Koller, Ulrich; Bauer, Johann

doi:10.5772/51926

Cited by 2 publications

(3 citation statements)

References 90 publications

(105 reference statements)

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“…In order to develop a 5′ trans-splicing-based therapy able to replace the coding sequence upstream of exon 16, we first designed the 154 nt BD, termed BD-4A, hybridizing to the endogenous Col7a1 exon15/intron15 junction. To investigate its functionality concerning accurate trans-splicing into Col7a1, we cloned it into our previously established RTM screening vector, 22,23 containing a red fluorescence protein (dsRED) as a reporter molecule, the 5′ half of green fluorescence protein (GFP) and a functional 5′ splice site. Additionally, we generated a HEK293 cell line stably expressing the Col7a1 target region exon15/intron15 and the missing 3′ GFP half to have a model system mimicking the endogenous setting.…”

Section: Proof Of Functionality Of the Bd Using A Fluorescencebased Smentioning

confidence: 99%

A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair

Peking

Koller

Hainzl

et al. 2016

Molecular Therapy - Nucleic Acids

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RNA trans-splicing represents an auspicious option for the correction of genetic mutations at RNA level. Mutations within COL7A1 causing strong reduction or absence of type VII collagen are associated with the severe skin blistering disease dystrophic epidermolysis bullosa. The human COL7A1 mRNA constitutes a suitable target for this RNA therapy approach, as only a portion of the almost 9 kb transcript has to be delivered into the target cells. Here, we have proven the feasibility of 5' trans-splicing into the Col7a1 mRNA in vitro and in vivo. We designed a 5' RNA trans-splicing molecule, capable of replacing Col7a1 exons 1-15 and verified it in a fluorescence-based trans-splicing model system. Specific and efficient Col7a1 trans-splicing was confirmed in murine keratinocytes. To analyze trans-splicing in vivo, we used gene gun delivery of a minicircle expressing a FLAG-tagged 5' RNA trans-splicing molecule into the skin of wild-type mice. Histological and immunofluorescence analysis of bombarded skin sections revealed vector delivery and expression within dermis and epidermis. Furthermore, we have detected trans-spliced type VII collagen protein using FLAG-tag antibodies. In conclusion, we describe a novel in vivo nonviral RNA therapy approach to restore type VII collagen expression for causative treatment of dystrophic epidermolysis bullosa.

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Section: Proof Of Functionality Of the Bd Using A Fluorescencebased Smentioning

confidence: 99%

A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair

Peking

Koller

Hainzl

et al. 2016

Molecular Therapy - Nucleic Acids

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“…There are four main types: Epidermolysis bullosa simplex (EBS), Dystrophic epidermolysis bullosa (DEB), Junctional epidermolysis bullosa (JEB), and Kindler syndrome (KS) (Fine and Hintner 2021) Based on symptoms the Epidermolysis bullosa (EB) genetically and clinically is characterized by blister formation and erosions of the skin and mucous membranes after minor trauma (Laimer et al, 2009). Mayr et al, (2013) suggest the inheritance of the affected genes can occur in a dominant or recessive way depending on the subform of the disease. The EBs is caused by gene mutations which encode proteins placed in basal membrane zone of the skin.…”

Section: Introductionmentioning

confidence: 99%

“…Mayr et al, (2013) report for mutations in the genes, encoding for the keratins 5 and 14 and plectin, lead to epidermolysis bullosa simplex (EBS) characterized by the cytolysis within basal keratinocytes. Loss function of laminin -332, collagen type XVII or integrin-β4 is shown to cause Junctional epidermolysis bullosa (JEB) which is subtype of EBs.…”

mentioning

confidence: 99%

Inheritance of the Epidermolysis Bullosa Subtypes

Temaj,

Gashi,

Beadini

et al. 2023

J. bioanthropol. (Online)

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Epidermolysis bullosa (EB) is a group of inherited disorders that cause skin to blister and tear easily. The disease is caused by mutations in structural proteins that are key for maintaining the integrity of the skin’s basement membrane zone or dermoepidermal junction. EB can be inherited in two ways: autosomal dominant and autosomal recessive. The most common form of EB, epidermolysis bullosa simplex (EBS), as well as some forms of dystrophic epidermolysis bullosa (DEB) are inherited in an autosomal dominant pattern. This means they are passed down from an affected parent to half of his or her children. Other forms of EB, such as junctional epidermolysis bullosa (JEB) and some forms of DEB, are inherited in an autosomal recessive pattern. This means that two copies of the mutated gene, one from each parent, are required to develop the condition.

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Gene Therapy for the COL7A1 Gene

Cited by 2 publications

References 90 publications

A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair

A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair

Inheritance of the Epidermolysis Bullosa Subtypes

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