Precision biotherapeutics is among the new revolutionary breakthroughs in modern medicine, that tailors to the individual genetic makeup of the patients providing personalized treatments to their otherwise noncurable ailments using tools like gene therapy and gene editing using biotechnology and bioinformatics.

AI gene editing the technology that couples artificial intelligence(AI) with gene editing (GED) techniques such as CRISPR-Cas9, ZENs, and TALENs AI. Gene editing has accelerated the pace of genomic studies, research, and development by enhancing precision, optimizing edits, improving specificity, and automating genomic analyses using its’ automated algorithms. Promising advancements in biological fields such as biomedical research, agriculture, and personalized medicine. Though ethical concerns about unintended effects and equitable access are significant of the process, AI gene editing is at the very edge of genomic research progress, providing unprecedented precision and versatility in modifying genetic information and analysis.

CRISPR and CRISPRcas9
Full form: Clustered Regularly Interspaced Short Palindromic Repeats,
CRISPR was first discovered in a bacterial immune system. Since then, CRISPRcas9 has been adapted into a powerful tool for genomic research due to its ability to be easily manipulated for the desired work,
consisting of 2 major parts:
A scissor Cas9 enzyme that cleaves or nicks the genome of interest
A bloodhound RNA guide (gRNA) that tethers the scissor protein to the target gene.

The steps for the process are as follows :
Recognition:
The CRISPR-Cas9 system includes a guide RNA (gRNA) that is programmed to recognize and bind to a specific sequence of DNA within the target genome. This sequence is complementary to the gRNA.
Binding:
Once bound to the target DNA sequence, the Cas9 enzyme forms a complex with the gRNA, creating a structure that is ready for DNA cleavage.
Cutting:
Cas9 acts as a molecular scissor and cuts both strands of the DNA at the targeted location. This creates a double-strand break (DSB) in the DNA.
Repair:
Cells have mechanisms to repair DNA breaks. One method, Non-Homologous End Joining (NHEJ), often introduces small insertions or deletions (indels) at the break site, disrupting the gene’s function. Alternatively, Homology-Directed Repair (HDR) can be utilized if a repair template is provided alongside CRISPR-Cas9, allowing precise modifications to be made.
Expression:
After repair, the edited DNA sequence can express a modified gene functionally, potentially altering cellular behavior or phenotype.
CRISPR in Therapeutics
The goal of AI gene editing is for scientists to be able to modify bacterium into mini-factories producing favorable proteins and other substances through gene expression and translation this can be achieved by AI’s designing and engineering abilities. These expressed proteins will then be used to tackle issues that the biotechnology industry has been facing for years. Integrating with AI softwares like ChatGPT, more than 700 million proteins have been sequenced and modeled.

CRISPR-Cas9 is being applied to develop genetic tests for identifying individuals at risk of developing certain fatal congenital(acquired from parental genome i.e genetic disorders) diseases. It can also be used to create novel gene-editing therapies for treating genetic disorders and cancer. The AI can forecast off-target effects of the causative agents and optimize the design of guide RNAs and Cas9 proteins, customizing them to specific requirements and pathways revolving the disorder.

CRISPR for Sickle cell anemia
One of the more recent accomplishments of CRISPR was in December of 2023, when the FDA approved two CRISPR-based therapies to treat sickle cell disease (SCD) in patients 12 years of age and older.
Sickle cell disease is a genetic disorder which is characterized by the production of abnormal hemoglobin (hemoglobin S), leading to abnormally shaped red blood cells (sickle-shaped in contrast to disc-shaped normal RBC) which causes pain, organ damage, and other complications due to the abnormal shape leading to improper functioning (inability to carry oxygen properly) and blockage in capillaries caused due to the clumping and aggregation of these sickle cells increasing the risk of stroke.

Researchers are exploring CRISPR-Cas9 technology to correct the genetic point mutation (a single nucleotide change in the HBB gene-substitution of a valine for glutamic acid as the seventh amino acid of the beta globin chain. ) responsible for sickle cell disease. The goal is to restore the production of normal hemoglobin (hemoglobin A) instead of hemoglobin S, thereby preventing the formation of sickle-shaped red blood cells.

Challenges
While CRISPR is a powerful tool in the diagnosis and cure of genetic disorders, However, the scientific community backtracked after the death of Jesse Gelsinger in 1999 at the age of 18 due to a massive immune reaction to the gene therapy he received. Since then, several studies have evaluated the efficacy and safety of human gene therapy to treat genetic disorders. And a set of problems that come in the way are ethical concerns regarding CRISPR-Cas9 for treating genetic disorders like sickle cell disease. These include potential off-target effects and the debate over germline versus somatic cell editing. Ensuring informed consent, addressing equitable access, and establishing effective regulation are critical. Social implications, such as impacts on human identity and cultural views on genetic modification, underscore the need for inclusive dialogue and careful consideration of broader societal impacts.

Conclusion
AI gene editing, fueled by the synergy of artificial intelligence and CRISPR-Cas9 technology, represents a transformative and dynamic frontier in genomic research. This integration enhances precision by optimizing edits, improving specificity, and automating genomic analyses. Promising significant advancements in the fields of biomedical research, agriculture, and personalized medicine. However, alongside its potential benefits, ethical considerations loom large, particularly concerning unintended effects, equitable access to treatments, and the broader societal impacts of genetic modification. Navigating these challenges will be crucial as we harness the full potential of CRISPR-Cas9 and AI in reshaping the landscape of genetic therapies and research in the future.

Sources: https://theconversation.com/ai-plus-gene-editing-promises-to-shift-biotech-into-high-gear-230183

https://theconversation.com/ai-plus-gene-editing-promises-to-shift-biotech-into-high-gear-230183

https://singularityhub.com/2023/03/21/metas-new-ai-is-digging-into-the-most-mysterious-proteins-on-earth/

https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1335901/full#h6

https://www.synthego.com/crispr-sickle-cell-disease#:~:text=Using%20CRISPR%20to%20restore%20adult,hemoglobin%20S)%20to%20be%20produced.

https://www.genome.gov/genetics-glossary/CRISPR

https://www.nhlbi.nih.gov/health/sickle-cell-disease

https://www.nature.com/collections/txhdfslxzh/posters

https://www.sciencedirect.com/science/article/abs/pii/S187711732100034X

Nishtha Shokeen

University/College name : Daulat Ram College