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Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion.

Annu Rev Biomed Eng

January 2025

1Center for Engineering for Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant.

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Introduction: Sarcomas are a rare and diverse group of mesenchymal-origin solid tumors, constituting only 1% of adult malignancies and classified into soft tissue and bone sarcomas. For localized disease, surgery and radiotherapy remain the cornerstone treatments. However, systemic options for advanced stages are limited, with an overall survival of approximately 20 months.

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Many new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) of human immunodeficiency virus type-1 (HIV-1) have been discovered in populations with multiple circulating HIV-1 genotypes. In this study, we report two novel URFs derived from two HIV-1-positive individuals in Hebei, China, who were infected through homosexual (BDD142) and heterosexual (BDD154) contact. Phylogenetic and recombinant analyses of the two NFLG revealed that they are second-generation recombinant strains originating from the CRF01_AE cluster 4/B and CRF01_AE cluster 5/B strains.

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Objectives: This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols.

Methods: We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways.

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The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease.

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