Vol 24, No 1 (2024)

Biobank involves collecting, processing, storing, and organizing biosamples, along with relevant personal and health information such as medical history, family records, genetics data, and lifestyle details, for medical research and clinical care. Oral biobanking is a recently evolved field alongside the rising of precision medicine due to recent research findings in oral oncology and other oral complaints, namely caries and periodontal disease. The common samples in oral biobanks are matured and primary teeth, dental pulp cells, oral biopsies, oral rinses, saliva, and swabs from the buccal region. Moreover, biobank should not conceive of as a static collection of samples and data but as a dynamic resource for developing novel techniques that meet current scientific demands through international networking. However, the major bottlenecks associated with oral biobanks are privacy, processing of samples, normalization of data, extended durability of interest markers of banked samples, and financial sustainability of biobanks. Thus in this correspondence, we argue that an alternative approach is urgently needed to protect the interests of many stakeholders.

Neuromuscular diseases are severe disorders affecting the peripheral nervous system, usually driving to death in a limited time. Many new drugs, through RNA-interference technology, are revolutionizing the prognosis and quality of life for these patients. Nevertheless, given the increased life expectancy, some new issues and phenotypes are expected to be revealed. In the transthyretin-mediated hereditary amyloidosis (ATTR-v, \"v\" for \"variant\"), the RNA interference was demonstrated to effectively reduce the hepatic synthesis of transthyretin, with a significant increase in disease progression in terms of polyneuropathy and cardiomyopathy. The increased life expectancy could promote the involvement of organs where the extra-hepatic transthyretin is deposited, such as the brain and eye, which are probably not targeted by the available treatments. All these issues are discussed in this editorial.

Abstracts:Duchenne and Becker muscular dystrophies are allelic X-linked recessive neuromuscular diseases affecting both skeletal and cardiac muscles. Therefore, owing to their single X chromosome, the affected boys receive pathogenic gene mutations from their unknowing carrier mothers. Current pharmacological drugs are palliative that address the symptoms of the disease rather than the genetic cause imbedded in the Dystrophin gene DNA sequence. Therefore, alternative therapies like gene drugs that could address the genetic cause of the disease at its root are crucial, which include gene transfer/implantation, exon skipping, and gene editing. Presently, it is possible through genetic reprogramming to engineer AAV vectors to deliver certain therapeutic cargos specifically to muscle or other organs regardless of their serotype. Similarly, it is possible to direct the biogenesis of exosomes to carry gene editing constituents or certain therapeutic cargos to specific tissue or cell type like brain and muscle. While autologous exosomes are immunologically inert, it is possible to camouflage AAV capsids, and lipid nanoparticles to evade the immune system recognition. In this review, we highlight current opportunities for Duchenne muscular dystrophy gene therapy, which has been known thus far as an incurable genetic disease. This article is a part of Gene Therapy of Rare Genetic Diseases thematic issue.

The success of gene therapy attempts is controversial and inconclusive. Currently, it is popular among the public, the scientific community, and manufacturers of Gene Therapy Medical Products. In the absence of any remedy or treatment options available for untreatable inborn metabolic orphan or genetic diseases, cancer, or brain diseases, gene therapy treatment by genoceuticals and T-cells for gene editing and recovery remains the preferred choice as the last hope. A new concept of "Genoceutical Gene Therapy" by using orphan ‘nucleic acid-based therapy’ aims to introduce scientific principles of treating acquired tissue damage and rare diseases. These Orphan Genoceuticals provide new scope for the ‘genodrug’ development and evaluation of genoceuticals and gene products for ideal ‘gene therapy’ use in humans with marketing authorization application (MAA). This perspective study focuses on the quality control, safety, and efficacy requirements of using ‘nucleic acid-based and human cell-based new gene therapy’ genoceutical products to set scientific advice on genoceutical-based ‘orphan genodrug’ design for clinical trials as per Western and European guidelines. The ethical Western FDA and European EMA guidelines suggest stringent legal and technical requirements on genoceutical medical products or orphan genodrug use for other countries to frame their own guidelines. The introduction section proposes less-- known ‘orphan drug-like’ properties of modified RNA/DNA, human cell origin gene therapy medical products, and their transgene products. The clinical trial section explores the genoceutical sources, FDA/EMA approvals for genoceutical efficacy criteria with challenges, and ethical guidelines relating to gene therapy of specific rare metabolic, cancer and neurological diseases. The safety evaluation of approved genoceuticals or orphan drugs is highlighted with basic principles and ‘genovigilance’ requirements (to observe any adverse effects, side effects, developed signs/symptoms) to establish their therapeutic use. Current European Union and Food and Drug Administration guidelines continuously administer fast-track regulatory legal framework from time to time, and they monitor the success of gene therapy medical product efficacy and safety. Moreover, new ethical guidelines on ‘orphan drug-like genoceuticals’ are updated for biodistribution of the vector, genokinetics studies of the transgene product, requirements for efficacy studies in industries for market authorization, and clinical safety endpoints with their specific concerns in clinical trials or public use.