Human genes lost and their functions found

Plenge, Robert M.

doi:10.1038/544171a

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…With the development of science and technology, genetic engineering has been gradually applied in the field of bone tissue engineering [151,152]. Genetic engineering, also known as gene-splicing technology or DNA recombination technology, is a complex technology that allows a gene to be replicated, transcribed, and translated in the recipient cell through in vitro recombination by manipulating the gene at the molecular level [153]. Knockout, which is a branch of genetic engineering, is an exogenous DNA introduction technique in which a DNA fragment containing a known sequence is homologously recombined with a gene of the same or similar sequence and incorporated into the genome of the recipient cell to be introduced into the tissue for expression.…”

Section: Gene Therapymentioning

confidence: 99%

The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering

You

Zhai

et al. 2023

IJMS

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The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site is a vital constraint that affects the regenerative effect, which is closely related to the degree of a well-established vascular network. Hypoxia-inducible factor (HIF-1α), which is an essential transcription factor activated in hypoxic environments, plays a vital role in vascular network construction. HIF-1α, which plays a central role in regulating cartilage and bone formation, induces vascular invasion and differentiation of osteoprogenitor cells to promote and maintain extracellular matrix production by mediating the adaptive response of cells to changes in oxygen levels. However, the application of HIF-1α in bone tissue engineering is still controversial. As such, clarifying the function of HIF-1α in regulating the bone regeneration process is one of the urgent issues that need to be addressed. This review provides insight into the mechanisms of HIF-1α action in bone regeneration and related recent advances. It also describes current strategies for applying hypoxia induction and hypoxia mimicry in bone tissue engineering, providing theoretical support for the use of HIF-1α in establishing a novel and feasible bone repair strategy in clinical settings.

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Section: Gene Therapymentioning

confidence: 99%

The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering

You

Zhai

et al. 2023

IJMS

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Therapeutic oligonucleotides in cardiovascular and metabolic diseases: insights for the internist

et al. 2018

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The idea of using small RNA fragments (oligonucleotides) for therapeutic purposes dates back to the 1990s, following the landmark discoveries on the mechanisms of gene silencing and RNA-interference (RNA-i). However, the first applications in medicine were hampered by difficulties in chemical stabilization and efficient delivery to target tissues. Recent advances in chemical manipulation of oligonucleotides have, at least partially, bypassed such obstacles. In particular, conjugation with ligands for specific receptors allows the selective uptake of oligonucleotides by critical cells (e.g., hepatocytes), where they inhibit the synthesis of the target protein by binding the complementary mRNA and inducing its degradation. In parallel, next-generation sequencing (NGS) studies at population levels have identified a number of key molecular targets, mainly through the discovery of "human knock-outs," i.e., subjects lacking a given protein because of nonsense mutations in the corresponding gene. Such highly informative individuals are often healthy, or even protected from the development of certain diseases. Indeed, subjects with null mutations in certain genes controlling lipoprotein metabolism like PCSK9 or ANGPTL-3 have a lower risk of cardiovascular disease. Since the complete absence of such proteins does not appear to carry any negative health effect, the corresponding genes are ideal candidates for the silencing approach. Pilot clinical trials with long acting anti-PCSK9 or anti-ANGPTL-3 oligonucleotides have yielded very promising results, so that their use as "vaccines" against atherosclerosis has been suggested in the future. As therapeutic oligonucleotides can virtually target innumerable proteins, their increasing development is predicted to substantially expand the repertoire of the "biological drugs," in addition to, or even substituting, more consolidated approaches like monoclonal antibodies.

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Human genes lost and their functions found

Cited by 2 publications

References 10 publications

The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering

The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering

Therapeutic oligonucleotides in cardiovascular and metabolic diseases: insights for the internist

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