Prenatal Gene Therapy

Schwab, Marisa E.; MacKenzie, Tippi C.

doi:10.1097/grf.0000000000000655

Cited by 9 publications

(10 citation statements)

References 70 publications

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“…IUFGT plans to deliver genes to cells and tissues early in prenatal life, offering the potential of prophylaxis, allowing the correction of a genetic defect before early irreparable tissue damage has occurred and, overall, improving postnatal clinical outcomes. In contrast to postnatal gene therapy, the prenatal application may offer several advantages: (i) the small fetal size allows for a higher vector-to-target-cell ratio to be achieved; (ii) the tolerogenic fetal immune system could limit anti-vector immune responses, often acquired in postnatal life, and could facilitate postnatal repeat vector administration if needed; (iii) the presence of highly proliferative and accessible stem/progenitor cells in multiple organs; (iv) the BBB is most permeable during early developmental stages, increasing brain transduction; and (v) the ability to treat disorders in which irreversible pathological metabolic and molecular changes begin before birth [166].…”

Section: In Utero Fetal Gene Therapymentioning

confidence: 99%

Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective

et al. 2022

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Mitochondrial diseases (MDs) are a group of severe genetic disorders caused by mutations in the nuclear or mitochondrial genome encoding proteins involved in the oxidative phosphorylation (OXPHOS) system. MDs have a wide range of symptoms, ranging from organ-specific to multisystemic dysfunctions, with different clinical outcomes. The lack of natural history information, the limits of currently available preclinical models, and the wide range of phenotypic presentations seen in MD patients have all hampered the development of effective therapies. The growing number of pre-clinical and clinical trials over the last decade has shown that gene therapy is a viable precision medicine option for treating MD. However, several obstacles must be overcome, including vector design, targeted tissue tropism and efficient delivery, transgene expression, and immunotoxicity. This manuscript offers a comprehensive overview of the state of the art of gene therapy in MD, addressing the main challenges, the most feasible solutions, and the future perspectives of the field.

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Section: In Utero Fetal Gene Therapymentioning

confidence: 99%

Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective

et al. 2022

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“…Since then, the interest in this field has grown [ 115 ], and nanoparticles have been exploited as carriers of nucleic acids in utero during embryonic or fetal life [ 116 , 117 , 118 , 119 ]. Although no human studies have been carried out until now for in utero gene therapy, many in vitro and in vivo studies have been performed [ 120 ]. In utero gene therapy is a potential game-changer for monogenic diseases because the treatment can prevent disease inception, avoiding early damage to the tissues.…”

Section: In Utero Gene Therapymentioning

confidence: 99%

“…Another advantage is the prevention of immune system reactions to the gene therapy approach, limiting or overcoming its effectiveness, as it occurs in post-natal genetic therapy. Other potential benefits are the capacity to cross the blood–brain barrier or deliver the treatment with a high vector-to-target-cell ratio [ 120 ].…”

Section: In Utero Gene Therapymentioning

confidence: 99%

“…The broad container of gene therapy comprises endogenous gene editing, gene replacement or augmentation, and the use of antisense oligonucleotides to regulate protein expression [ 120 ]. However, these techniques bring some risks, such as insertional mutagenesis (observed in post-natal treatment) or the threat of germline transfer.…”

Section: In Utero Gene Therapymentioning

confidence: 99%

“…An example of insertional mutagenesis was the development of T-cell leukemia several years after gene therapy for X-linked severe combined immunodeficiency in four patients [ 121 ]. In these four cases, the retroviral vector had inserted within the LMO-2 locus, which is known to be involved in T-cell leukemia development [ 120 , 121 ]. However, the potential is high, and preclinical studies focus on various pathologies such as spinal muscular atrophy, thalassemia, neuronopathic Gaucher disease, congenital retinal blindness, and cystic fibrosis [ 120 ].…”

Section: In Utero Gene Therapymentioning

confidence: 99%

See 2 more Smart Citations

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

Bertozzi

Corradetti

Seriau

et al. 2022

JPM

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Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies.

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Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI‐FDA Meeting)

Herzeg

Almeida‐Porada

Charo³

et al. 2022

The Journal of Clinical Pharma

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We are living in a golden age of medicine in which the availability of prenatal diagnosis, fetal therapy, and gene therapy/editing make it theoretically possible to repair almost any defect in the genetic code. Furthermore, the ability to diagnose genetic disorders before birth and the presence of established surgical techniques enable these therapies to be delivered safely to the fetus. Prenatal therapies are generally used in the second or early third trimester for severe, life-threatening disorders for which there is a clear rationale for intervening before birth. While there has been promising work for prenatal gene therapy in preclinical models, the path to a clinical prenatal gene therapy approach is complex. We recently held a conference with the University of California, San Francisco-Stanford Center of Excellence in Regulatory Science and Innovation, researchers, patient advocates, regulatory (members of the Food and Drug Administration), and other stakeholders to review the scientific background and rationale for prenatal somatic cell gene therapy for severe monogenic diseases and initiate a dialogue toward a safe regulatory path for phase 1 clinical trials. This review represents a summary of the considerations and discussions from these conversations.

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Prenatal Gene Therapy

Cited by 9 publications

References 70 publications

Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective

Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI‐FDA Meeting)

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