Editing Human genetic enhancement (section)

== Disease treatment ==

=== Gene therapy ===
{{Main|Gene therapy}}

Modification of human genes in order to treat genetic diseases is referred to as [[gene therapy]]. Gene therapy is a medical procedure that involves inserting genetic material into a patient's cells to repair or fix a malfunctioning gene in order to treat hereditary illnesses. Between 1989 and December 2018, over 2,900 [[clinical trial]]s of gene therapies were conducted, with more than half of them in [[Phases of clinical research|phase I]].<ref name="JGenMed Database">{{cite web |date=June 2016 |title=Gene Therapy Clinical Trials Worldwide Database |url=https://a873679.fmphost.com/fmi/webd/GTCT |work=The Journal of Gene Medicine }}s</ref> Since that time, many gene therapy based drugs became available, such as [[Zolgensma]] and [[Patisiran]]. Most of these approaches utilize [[viral vector]]s, such as [[adeno-associated virus]]es (AAVs), adenoviruses (AV) and [[lentivirus]]es (LV), for inserting or replacing [[transgene]]s ''[[in vivo]]'' or ''[[ex vivo]]''.<ref>{{cite journal | vauthors = Li X, Le Y, Zhang Z, Nian X, Liu B, Yang X | title = Viral Vector-Based Gene Therapy | journal = International Journal of Molecular Sciences | volume = 24 | issue = 9 | page = 7736 | date = April 2023 | pmid = 37175441 | pmc = 10177981 | doi = 10.3390/ijms24097736 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lundstrom K | title = Viral Vectors in Gene Therapy: Where Do We Stand in 2023? | journal = Viruses | volume = 15 | issue = 3 | page = 698 | date = March 2023 | pmid = 36992407 | pmc = 10059137 | doi = 10.3390/v15030698 | doi-access = free }}</ref>

In 2023, [[nanoparticle]]s that act similarly to viral vectors were created. These nanoparticles, called ''bioorthgonal engineered virus-like recombinant biosomes'', display strong and rapid binding capabilities to [[LDL receptor]]s on cell surfaces, allowing them to enter cells efficiently and [[gene delivery|deliver genes]] to specific target areas, such as [[Neoplasm|tumor]] and [[Arthritis|arthritic tissues]].<ref>{{cite journal | vauthors = Bao CJ, Duan JL, Xie Y, Feng XP, Cui W, Chen SY, Li PS, Liu YX, Wang JL, Wang GL, Lu WL | display-authors = 6 | title = Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy | journal = Nano-Micro Letters | volume = 15 | issue = 1 | pages = 197 | date = August 2023 | pmid = 37572220 | pmc = 10423197 | doi = 10.1007/s40820-023-01153-y | bibcode = 2023NML....15..197B }}</ref>

[[RNA interference]]-based agents, such as [[zilebesiran]], contain [[Small interfering RNA|siRNA]] which binds with mRNA of the target cells, modifying gene expression.<ref>{{cite journal | vauthors = Desai AS, Webb DJ, Taubel J, Casey S, Cheng Y, Robbie GJ, Foster D, Huang SA, Rhyee S, Sweetser MT, Bakris GL | display-authors = 6 | title = Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension | journal = The New England Journal of Medicine | volume = 389 | issue = 3 | pages = 228–238 | date = July 2023 | pmid = 37467498 | doi = 10.1056/NEJMoa2208391 | hdl = 20.500.11820/9ec1c393-058a-4fe7-8e8f-df207dcdfb85 | s2cid = 259995680 | url = https://openaccess.sgul.ac.uk/id/eprint/115616/1/nejmoa2208391.pdf | hdl-access = free }}</ref>

=== CRISPR/Cas9 ===
{{Main | CRISPR gene editing}}

Many diseases are complex and cannot be effectively treated by simple coding sequence-targeting strategies. CRISPR/Cas9 is one technology that targets double strand breaks in the human genome, modifying genes and providing a quick way to treat genetic disorders. Gene treatment employing the CRISPR/Cas genome editing method is known as CRISPR/Cas-based gene therapy. Mammalian cells can be genetically modified using the straightforward, affordable, and extremely specific CRISPR/Cas method. It can help with single-base exchanges, homology-directed repair, and non-homologous end joining. The primary application is targeted gene knockouts, involving the disruption of coding sequences to silence deleterious proteins. Since the development of the CRISPR-Cas9 gene editing method between 2010 and 2012, scientists have been able to alter genes by making specific breaks in their DNA. This technology has many uses, including [[genome editing]] and molecular diagnosis.

Genetic engineering has undergone a revolution because to CRISPR/Cas technology, which provides a flexible framework for building disease models in larger animals. This breakthrough has created new opportunities to evaluate possible therapeutic strategies and comprehend the genetic foundations of different diseases. But in order to fully realize the promise of CRISPR/Cas-based gene therapy, a number of obstacles must be removed. Improving CRISPR/Cas systems' editing precision and efficiency is one of the main issues. Although this technology makes precise gene editing possible, reducing off-target consequences is still a major challenge. Unintentional genetic changes resulting from off-target modifications may have unanticipated effects or difficulties. Using enhanced guide RNA designs, updated Cas proteins, and cutting-edge bioinformatics tools, researchers are actively attempting to improve the specificity and reduce off-target effects of CRISPR/Cas procedures. Moreover, the effective and specific delivery of CRISPR components to target tissues presents another obstacle. Delivery systems must be developed or optimized to ensure the CRISPR machinery reaches the intended cells or organs efficiently and safely. This includes exploring various delivery methods such as viral vectors, nanoparticles, or lipid-based carriers to transport CRISPR components accurately to the target tissues while minimizing potential toxicity or immune responses.

Despite recent progress, further research is needed to develop safe and effective CRISPR therapies. CRISPR/Cas9 technology is not actively used today, however there are ongoing clinical trials of its use in treating various disorders, including sickle cell disease, human papillomavirus (HPV)-related cervical cancer, COVID-19 respiratory infection, renal cell carcinoma, and multiple myeloma.<ref name="pmid36988873">{{cite journal | vauthors = Sinclair F, Begum AA, Dai CC, Toth I, Moyle PM | title = Recent advances in the delivery and applications of nonviral CRISPR/Cas9 gene editing | journal = Drug Delivery and Translational Research | volume = 13 | issue = 5 | pages = 1500–19 | date = May 2023 | pmid = 36988873 | pmc = 10052255 | doi = 10.1007/s13346-023-01320-z }}</ref>

[[Gene therapy]] has emerged as a promising field in [[medical science]], aiming to address and treat various [[genetic diseases]] by modifying [[human genes]]. The process involves the introduction of genetic material into a patient's cells, with the primary goal of repairing or correcting malfunctioning genes that contribute to [[Heredity|hereditary illnesses]]. This innovative medical procedure has seen significant advancements and a growing number of clinical trials since its inception.

Between 1989 and December 2018, more than 2,900 clinical trials of gene therapies were conducted, with over half of them reaching the phase I stage. Over the years, several gene therapy-based drugs have been developed and made available to the public, marking important milestones in the treatment of [[genetic disorder]]s. Examples include Zolgensma and Patisiran, which have demonstrated efficacy in addressing specific genetic conditions.

The majority of gene therapy approaches leverage viral vectors, such as adeno-associated viruses (AAVs), adenoviruses (AV), and lentiviruses (LV), to facilitate the insertion or replacement of transgenes either in vivo or ex vivo. These vectors serve as delivery vehicles for introducing the therapeutic genetic material into the patient's cells.

A notable development in 2023 was the creation of [[nanoparticle]]s designed to function similarly to viral vectors. These bioorthogonal engineered virus-like recombinant biosomes represent a novel approach to gene delivery. They exhibit robust and rapid binding capabilities to low-density lipoprotein (LDL) receptors on cell surfaces, enhancing their efficiency in entering cells. This capability enables the targeted delivery of genes to specific areas, such as tumor and arthritic tissues. This advancement holds the potential to enhance the precision and effectiveness of gene therapy, minimizing off-target effects and improving overall therapeutic outcomes.

In addition to viral vector and nanoparticle-based approaches, RNA interference (RNAi) has emerged as another strategy in gene therapy. Agents like zilebesiran utilize small interfering RNA (siRNA) that binds with the messenger RNA ([[mRNA]]) of target cells, effectively modifying gene expression. This RNA interference-based approach provides a targeted and specific method for regulating gene activity, presenting further opportunities for treating [[genetic disorder]]s.

The continuous evolution of [[gene therapy |gene therapy techniques]], along with the development of innovative delivery systems and therapeutic agents, underscores the ongoing commitment of the scientific and medical communities to advance the field and provide effective treatments for a wide range of genetic diseases.
<ref>{{cite journal |vauthors=Amador C, Shah R, Ghiam S, Kramerov AA, Ljubimov AV |title=Gene Therapy in the Anterior Eye Segment |journal=Curr Gene Ther |volume=22 |issue=2 |pages=104–131 |date=2022 |pmid=33902406 |pmc=8531184 |doi=10.2174/1566523221666210423084233 }}</ref>