The genomic size, complexity, heritability, and diversity of human primary genetic compartments vary. Although the nuclear genome's huge size ensures that hundreds of reported monogenic diseases appear in a range of conditions, germline abnormalities in the mitochondrial and nuclear genomes often generate developmental issues. Accumulation of somatic mutations in the nuclear genome causes cancer, and somatic mutations in mitochondria may contribute to aging. More broadly, the microbial metagenome develops largely after birth, and is marked throughout their lifetimes by much more diversity and diversity among individuals. Mitochondrial sequencing, clinical exome and full-genome sequencing, and 16S and unbiased microbiological sequencing have all become more widely available because of developments in DNA sequencing next-generation.These technologies discover genetic defects that can be addressed with gene therapy. Modern aided techniques of reproduction, such as mitochondrial replacement therapy and preimplantation diagnosis, may address complete genomic compartments in bulk, such as mitochondrial and nuclear genomes. Additive somatic cell gene therapies started with the invention of viral vectors to infect human somatic cells that could be cultured ex vivo, such as T cells, and rapidly advanced to in vivo applications employing viral pseudotypes with specific tissue tropisms. CRISPR/Cas9 and other targeted gene editing approaches that fix the specific causative mutation or gene at its endogenous locus have recently expanded the possibility for more refined ex vivo and in vivo gene therapies.DNA sequencing costs have decreased during the past two decades, hurrying to identify genetic diseases. Targeted gene editing progress has now enabled the synthesis and testing of specific therapeutic reagents to address direct and accessible genetic abnormalities, repeating these diagnostic accomplishments. Generalized methods for delivering customizable gene editing reagents to the cell type and genomic compartment of interest in the specific genetic disease of a patient are one of the major outstanding challenges to wide-spread gene therapy. Aside from direct genetic disease repair, recent methods for rapidly identifying synthetic genetic circuits capable of improving cellular function in diseases such as cancer and autoimmune hold the promise of future gene therapy in modified somatic cells.Genetic diseases are becoming more readily diagnosed in all human genetic compartments, and the next generation of gene therapy platforms targeting each compartment are preparing to give flexible, tailored curative medicines. The Mitochondrial genome, nuclear genome, and microbial metagenome are the three genetic compartments present in humans. Gene therapies for each of these compartments come into three categories: whole genome replacement or selection, non-focused insertion of new genetic information to compensate for genetic errors, and direct gene editing to correct causative genetic disorders. The mitochondrial and nuclear genomes are determined at conception, save for somatic mutations and the adaptive immune receptor repertoire, and remain stable throughout life.
Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies