CRISPR: The Not So Far Future of Gene Editing

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Imagine a technology so precise it can act like molecular scissors, editing the very blueprint of life. That is precisely CRISPR—an acronym for “Clustered Regularly Interspaced Short Palindromic Repeats.” Originally discovered in bacteria as a defense mechanism, CRISPR has evolved into a gene-editing tool that offers unparalleled accuracy in genetic modification.?

CRISPR allows scientists to edit genes with unprecedented precision and efficiency, opening up new possibilities in medicine, agriculture, and environmental science.?

With the advent of AI writing, I’ve been cautious about using words like transformative, revolutionary, and groundbreaking. Yet, these are the precise words to accurately describe the advent of CRISPR in genetic engineering. Groundbreaking. Transformative. Revolutionary.

Today's Agenda

• CRISPR Implementations: Medical, Agricultural, and Environmental
• Successful Applications
• A Short Story
• Demystifying Jargon/How CRISPR Works
• Invest in CRISPR
• Challenges and Regulatory Framework
• Suggested Resources
• Sources Cited

Medical

• Genetic Disorders: CRISPR has the potential to cure hereditary diseases like cystic fibrosis and sickle cell anemia by directly correcting genetic mutations. Current research is promising, but widespread clinical applications are still in development. Potential approval for treatments is expected within the next five to ten years.
• Cancer Therapy: CRISPR is used to develop targeted cancer treatments by editing genes in cancer cells or engineering immune cells to attack tumors. Some therapies are already in clinical trials, and broader applications are anticipated within the next five years.
• Reproductive Medicine: Editing genes in embryos to prevent inherited diseases is a contentious area with significant ethical concerns. While research is ongoing, broad clinical use is likely several years away, depending on regulatory and ethical developments.

Agricultural

• Crop Improvement: CRISPR can enhance crop resilience and nutritional content. Advances are ongoing, with some CRISPR-edited crops nearing commercial release in the next few years.
• Sustainable Agriculture: The technology could reduce the need for chemical inputs, contributing to more eco-friendly farming practices. This potential is being explored, with practical applications expected in the next five to ten years.

Environmental

• Climate Change Mitigation: CRISPR may help engineer organisms that capture and store carbon dioxide. This research is in the early stages, with practical implementations likely a decade or more away.
• Invasive Species Control: Gene drives developed with CRISPR could manage invasive species, though this area is still experimental and requires more research, with potential applications in the next five to ten years.
• Conservation Efforts: CRISPR could aid in the protection and revival of endangered species. While promising, this application is still in the research phase and may take a decade or more to achieve practical results.

CRISPR technology has been successfully administered in various contexts, including clinical trials and research studies. Here are some key examples of its successful application:

Genetic Disorders

• Sickle Cell Disease and Beta-Thalassemia: Clinical trials have used CRISPR to edit the genes of patients with sickle cell disease and beta-thalassemia. By modifying the patient's stem cells to correct the genetic mutations causing these disorders, researchers have achieved promising results, including long-term remission of symptoms.

Source: Lin et al., (2017). https://doi.org/10.1182/BLOOD.V130.SUPPL_1.284.284.

• Beta-Globin Gene Targeting: CRISPR-based gene-editing platform effectively targets the HBB gene in human hematopoietic stem cells, potentially advancing next-generation therapies for b-hemoglobinopathies.

Source: Dever & Porteus, (2016). https://doi.org/10.1182/BLOOD.V128.22.2310.2310.

• Cystic Fibrosis: Recent research has focused on using CRISPR to target and modify the CFTR gene mutations that cause cystic fibrosis. Early studies suggest the potential to correct these mutations in lung epithelial cells, offering hope for a therapeutic approach that could ameliorate pulmonary symptoms and improve quality of life.

Source: Suzuki et al. (2020). https://doi.org/10.1016/j.ymthe.2020.04.021.

Cancer Treatment

• CAR-T Cell Therapy: CRISPR has been used to enhance CAR-T cell therapies, where immune cells are engineered to better target and destroy cancer cells. These therapies have shown effectiveness in treating certain types of leukemia and lymphoma.

Source: Wang et al. (2020). https://doi.org/10.1158/2159-8290.cd-20-1243.

• Glioblastoma: Researchers are investigating the use of CRISPR to disrupt genes that contribute to the growth and survival of glioblastoma cells. This approach aims to weaken the cancer cells, making them more susceptible to conventional treatments like chemotherapy and radiation.

Source: Bryan D Choi et al. (2019). https://doi.org/10.1186/s40425-019-0806-7.

Inherited Diseases

• Leber Congenital Amaurosis: In a landmark study, CRISPR was used to treat a rare genetic form of blindness called Leber congenital amaurosis. The therapy involved directly editing the DNA within the eye, and early results have shown improvements in vision.

Source: Morgan L. Maeder et al.? (2019). https://doi.org/10.1038/s41591-018-0327-9.

• Duchenne Muscular Dystrophy: CRISPR techniques are being developed to correct mutations in the dystrophin gene responsible for Duchenne muscular dystrophy. This genetic editing has the potential to restore muscle function in affected individuals, with several studies demonstrating success in animal models.

Source: Yi-Li Min et al. (2019). https://doi.org/10.1146/annurev-med-081117-010451.

HIV Research

• HIV Resistance: Researchers have used CRISPR to modify immune cells to make them resistant to HIV. Trials are ongoing to evaluate the long-term effectiveness and safety of this approach.

Source: HyunJun Kang et al. (2015).? https://doi.org/10.1038/mtna.2015.42.

Amber perched on the edge of the examination table, her fingers tracing absent patterns on the crisp paper beneath her. The sterile white walls seemed to close in, their clinical blankness a stark contrast to the tumultuous palette of emotions swirling within her. Overhead, fluorescent lights hummed a discordant lullaby, casting harsh shadows that accentuated the hollows beneath her eyes—eyes that had become both a source of torment and fascination.

A chart on the wall caught her attention: the human eye, dissected and labeled with clinical precision. Amber found herself drawn to the illustration of the iris, that delicate flower of pigment that defined so much of how the world perceived her. How strange, she thought, that such a small part of oneself could carry such weight.

The door's hinges released a plaintive whine as Dr. Huxley entered. His presence filled the room with a warmth that seemed at odds with the austere surroundings. But his genuine and reassuring smile did little to quell the rebellion in Amber's stomach.

"It's nothing serious, you know," the doctor stated, his voice a soothing balm to her frayed nerves.

"What?" Amber's response was barely audible, a wisp of sound carried on a shaky exhale.

Dr. Huxley settled onto a nearby stool, his eyes meeting hers with a mixture of compassion and clinical interest. "It's nothing different than dyeing your hair or getting your ears pierced," he offered, his tone suggesting he'd had this conversation many times before.

But Amber's mother's words still echoed in her mind, a mantra of doubt and disapproval: "Edit your genes? Pfft, if God wanted you to have blue eyes, he would have given you blue eyes." The memory stung, a fresh wound in an already tender psyche.

"How exactly does it work?" Amber asked, desperate to drown out her internal cacophony with the doctor's explanation.

Dr. Huxley delved into the intricacies of the procedure: "Well, we've successfully identified the gene responsible for your specific eye color. In your case, it's the OCA2 gene. This gene influences the production of melanin in the iris, which determines how dark or light your eyes are. Now, all we need to do is administer a small injection into the subretinal space of your eye."—Amber's eyes widened slightly. "What's inside the shot?" she asked.

"Inside the injection, there's a very small, precise tool called Cas9, which acts like a pair of tiny scissors. Along with it, there's something we call guide RNA, which functions like a GPS system. The guide RNA leads the Cas9 to the exact spot in your DNA that we want to modify. Once there, the Cas9 makes a cut, and then we introduce a new DNA template to alter the melanin production in your iris." Dr. Huxley explained.

Amber found herself adrift in a sea of scientific jargon.

The needle approached, a silvery harbinger of change. Amber's breath caught in her throat, her heartbeat a thunderous tattoo against her ribs. A momentary sting, a strange tingling sensation, and it was done. The future altered in the blink of an eye—or rather, the injection of one.

Unable to contain her anticipation, Amber rushed to the mirror, her reflection a familiar stranger. But, the same unchanged hazel eyes started back at her. "It didn't work?" she whispered devastatingly.

Dr. Huxley chuckled: "The changes won't happen immediately," he explained . "It could take weeks, even months before you start seeing the difference."

Amber turned from her reflection, suddenly uncertain of the face that would eventually greet her in the mirror and thought to herself:

Is this really just like dying my hair?

Is it? Let me know in the comments below!

DNA?

• What it is: DNA is the molecule that carries the genetic instructions for life. It's made of two twisted strands that look like a ladder. The "rungs" of this ladder are made of four chemicals called bases. The sequence of these bases encodes all of our genetic information.?
• DNA Location: DNA is located in the nucleus of cells. Every cell in your body contains DNA, which is the same in all cells, whether it’s from your skin, blood, or brain.?

RNA

• What it is: RNA is a molecule similar to DNA but serves different functions in the cell. Unlike DNA, RNA is usually single-stranded. RNA's main role is to help convert the genetic information in DNA into proteins.?

Guide RNA

• What It Is: Guide RNA (gRNA) is a short, synthetic strand of RNA, similar to a small piece of genetic code. It is a molecule created in the lab.
• How It Works: gRNA guides the CRISPR-associated protein (such as Cas9) to a particular DNA sequence within a genome. Think of it as a GPS that guides the editing tool (Cas9 protein) to the right location to cut in the DNA.?
• How It’s Delivered: The guide RNA is mixed with other CRISPR components in the lab and delivered into cells using methods like viral vectors or nanoparticles.

?Cas9 Protein

• What It Is: Molecular “scissors” that cut the DNA at the exact spot indicated by the guide RNA. Once the DNA is cut, scientists can either insert new genetic material or remove unwanted sequences.
• How It Works: The Cas9 protein binds to the DNA at the site where the guide RNA has directed it and then makes a cut in the DNA strand. This cut allows for new genetic material to be inserted or unwanted sequences to be removed.
• How It’s Delivered: Similar to guide RNA, the Cas9 protein is delivered into cells along with the guide RNA using methods such as viral vectors, nanoparticles, or electroporation.

Virus

• What It Is: A virus is a microscopic infectious agent that can only replicate inside the living cells of a host organism. Viruses cannot reproduce on their own. They are made up of genetic material (either DNA or RNA) encased in a protein.?
• How It Works: Viruses attach to a host cell and hijack it with their genetic material. They replicate themselves and produce viral proteins, often destroying the host cell in the process. The new viruses then repeat the process on other cells, spreading the infection.?
• In the Context of CRISPR: Viruses can be used as vectors to deliver the CRISPR-Cas9 components into target cells. The CRISPR system was originally discovered as a bacterial immune mechanism against viruses. Bacteria use CRISPR sequences to recognize and cut viral DNA, preventing infection. This natural defense mechanism has been adapted for use in gene editing technologies.

. Delivery Methods

• Viral Vectors: Viruses are modified to carry CRISPR components into cells. The virus delivers the CRISPR system into the cell’s nucleus, where the editing happens.
• Nanoparticles: Tiny particles can also be used to deliver CRISPR components directly into cells. They are designed to cross cell membranes and release the CRISPR system inside.
• Electroporation: This technique uses an electric field to create tiny pores in the cell membrane, allowing CRISPR components to enter the cell.

Editing Process

• Targeting: The guide RNA finds and binds to the specific DNA sequence that needs editing.
• Cutting: The Cas9 protein makes a cut in the DNA at the targeted location.
• Repairing: The cell’s natural repair mechanisms then fix the break. Scientists can use this opportunity to insert new genetic material or delete unwanted sequences.
• Pre-Programmed Design: The guide RNA and Cas9 protein are pre-programmed in the lab. Once introduced into the cells, they execute their tasks based on their genetic instructions.?

Verification and Screening

• Sequencing: After editing, scientists often sequence the DNA to check if the changes were made accurately and if no unintended edits occurred.
• Functional Tests: Researchers also test the edited cells to ensure that the desired genetic changes produce the intended effects without causing adverse outcomes.

Creating the Viral Vectors

• Modification: Scientists first modify viruses in the lab to carry the CRISPR components (guide RNA and Cas9 protein). These viruses are engineered to be safe and not cause disease.
• Incorporation: The guide RNA and Cas9 protein are packaged into the virus. The virus acts as a delivery system, carrying these components into the cells.

Administration

• Injection: The modified virus is introduced into the body through an injection. Depending on the target cells or tissues, this can be done through various methods, such as intravenous (IV) injection, local injection into tissues, or other delivery routes.
• Infection: Once inside the body, the virus infects the target cells, effectively delivering the CRISPR components (guide RNA and Cas9 protein) into the cell’s interior.

Guide RNA Action

• Guiding: Once inside the cell, the guide RNA (gRNA) binds to the specific DNA sequence it’s designed to target.
• Function: The gRNA directs the Cas9 protein to the correct location in the DNA. The interaction between the gRNA and the target DNA sequence is highly specific, based on complementary base pairing.

Cas9 Protein Action

• Cutting: The Cas9 protein, guided by the gRNA, makes a precise cut in the DNA at the targeted location. This cut allows for the editing of the genetic material.

Cellular Repair

• Repair Mechanism: After the DNA is cut, the cell’s natural repair mechanisms come into play. Scientists can influence this repair process by either inserting new genetic material or removing unwanted sequences.

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Now that you've already invested, it's a perfect time to go over challenges and regulatory frameworks.

?Technical Challenges:?

• Precision and Off-Target Effects: Ensuring CRISPR's precision and minimizing unintended genetic changes are significant challenges. Ongoing research aims to improve the accuracy of the technology.
• Delivery Mechanisms: Efficiently delivering CRISPR components into cells remains a challenge. Various methods, including viral vectors and nanoparticles, are being developed and tested.

Ethical and Social Challenges:?

• Genetic Modifications: Ethical concerns include the potential for "designer babies" and the socio-economic divide in accessing genetic enhancements.
• Environmental Impact: The potential ecological consequences of gene drives and other environmental applications must be carefully considered.

Regulatory Frameworks:?

• National Regulations: Different countries have varying regulations for CRISPR applications. For example, the U.S. Food and Drug Administration (FDA) regulates clinical uses, while the European Union has strict guidelines for genetic modification.

International Guidelines: Efforts are underway to establish international standards for CRISPR use, particularly in clinical and environmental applications. Organizations like the World Health Organization (WHO) are involved in these discussions.

Overall Assessment:

Technological Feasibility Index (TFI): 9 - Reason: CRISPR technology is highly advanced and has been successfully used in various applications, including gene editing, medical research, and agriculture.

Societal Integration Quotient (SIQ): 7 - Reason: While CRISPR is making significant strides, its integration into everyday medical and agricultural practices faces ethical, regulatory, and public acceptance challenges.

Market Demand Coefficient (MDC): 8 - Reason: There is strong interest from the medical, agricultural, and biotech industries, driven by the potential to address genetic disorders, improve crop resilience, and develop new treatments.

CRISPR Overall: 8 ? Very Bullish

Suggested Resources

?? Experts

1. Jennifer Doudna - A biochemist at the University of California, Berkeley, Doudna co-discovered the CRISPR-Cas9 gene-editing technology, which has revolutionized genetics.
2. Emmanuelle Charpentier - Along with Jennifer Doudna, Charpentier is credited with the co-discovery of the CRISPR-Cas9 technology. She is affiliated with the Max Planck Institute for Infection Biology in Berlin.
3. Feng Zhang - A researcher at the Broad Institute of MIT and Harvard, Zhang has played a major role in adapting CRISPR for use in mammalian cells.
4. George Church - A professor at Harvard and MIT, Church's work spans various aspects of genetic engineering, including gene editing technologies.
5. Luhan Yang - Co-founder of Qihan Biotech, Yang focuses on using CRISPR to improve human health and agriculture.

?? YouTubers

1. Kurzgesagt – In a Nutshell: YouTube Channel - This channel creates high-quality animated videos that explain complex scientific concepts, including gene editing and CRISPR, in simple terms.
2. Veritasium: YouTube Channel - Run by Derek Muller, this channel delves into science, education, and technology topics through engaging videos. Veritasium has covered topics related to genetics and new technology in biology.
3. SciShow: YouTube Channel - Hosted by Hank Green and others, SciShow tackles questions about science, history, and biotechnology, including explanations of gene editing technologies.
4. TED-Ed: YouTube Channel - TED-Ed creates educational videos, including those on genetics and CRISPR, making complex topics accessible to a broader audience.
5. Armando Hasudungan: YouTube Channel - Specializes in biology and medicine videos, often including detailed illustrations. His videos on genetics and molecular biology are particularly insightful for students and enthusiasts.
6. iBiology - YouTube Channel This channel provides videos by leading biologists, and has several talks and discussions about CRISPR and its implications in biology and medicine.

?? Books

• "Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing" by Kevin Davies*: A comprehensive overview of CRISPR technology and its implications.
• "A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution" by Jennifer A. Doudna and Samuel H. Sternberg*: Insights from one of CRISPR's pioneers on its transformative potential.
• The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race by Walter Isaacson

?? Journals and Publications

• Nature Biotechnology - Journal Website
• Science - Journal Website
• Annual Reviews of Biotechnology - Journal Website

?? Scientific Papers and Articles

1. Ran, F., Hsu, P., Wright, J. et al. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8, 2281–2308 (2013). https://doi.org/10.1038/nprot.2013.143
2. Joy Y. Wang, Jennifer A. Doudna CRISPR technology: A decade of genome editing is only the beginning.Science379,eadd8643(2023).DOI:10.1126/science.add8643
3. Barrangou, R., Doudna, J. Applications of CRISPR technologies in research and beyond. Nat Biotechnol 34, 933–941 (2016). https://doi.org/10.1038/nbt.3659
4. Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering CRISPR: a review of the challenges and approaches. Drug Delivery, 25(1), 1234–1257. https://doi.org/10.1080/10717544.2018.1474964
5. Kaminski, M.M., Abudayyeh, O.O., Gootenberg, J.S. et al. CRISPR-based diagnostics. Nat Biomed Eng 5, 643–656 (2021). https://doi.org/10.1038/s41551-021-00760-7
6. Lander, E. S. (2016). The Heroes of CRISPR. Cell, 164(1-2), 18-28.2016). https://doi.org/10.1016/j.cell.2015.12.041

?? Websites and Online Resources

• Broad Institute CRISPR (https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr): The Broad Institute's resource page on CRISPR research and developments.
• CRISPR Therapeutics (https://www.crisprtx.com/): Information on CRISPR applications in medicine and therapy.

?? Videos and Documentaries

1. PBS NOVA: "The Gene: An Intimate History" – A documentary exploring the history and impact of gene-editing technologies.
2. Genetic Engineering Will Change Everything Forever – CRISPR - Designer babies, the end of diseases, genetically modified humans that never age. Outrageous things that used to be science fiction are suddenly becoming reality.
3. Biologist Explains One Concept in 5 Levels of Difficulty - CRISPR | WIRED - CRISPR is a new area of biomedical science that enables gene editing and could be the key to eventually curing diseases like autism or cancer. WIRED has challenged biologist Neville Sanjana to explain this concept to 5 different people; a 7 year-old, a 14 year-old, a college student, a grad student and a CRISPR expert.
4. Jennifer Doudna | Four ways that CRISPR will revolutionize healthcare - Hear from Nobel laureate Jennifer Doudna on the four ways that CRISPR gene editing technologies will revolutionize healthcare.
5. CRISPR and the Future of Human Evolution | Be Smart - Now that genetic engineering tools like CRISPR allow us to edit our genes, how will that impact human evolution going forward? Are designer babies or eugenics around the corner? Welcome to a world of nonrandom mutation and unnatural selection.

?? TedTalks

1. (2016) How CRISPR lets you edit DNA - Andrea M. Henle - Explore the science of the groundbreaking technology for editing genes, called CRISPR- Cas9, and how the tool could be used to cure diseases.
2. (2017) What you need to know about CRISPR | Ellen Jorgensen - Should we bring back the wooly mammoth? Or edit a human embryo? Or wipe out an entire species that we consider harmful?
3. (2023) CRISPR's Next Advance Is Bigger Than You Think | Jennifer Doudna | TED - You've probably heard of CRISPR, the revolutionary technology that allows us to edit the DNA in living organisms. Biochemist and 2023 Audacious Project grantee Jennifer Doudna earned the Nobel Prize for her groundbreaking work in this field -- and now she's here to tell us about its next world-changing advancement.
4. (2024) The Age of CRISPR: Engineering the Future of Genetic Medicine | Benjamin Oakes | TEDxBerkeley - Dr. Benjamin Oakes delves into the fascinating potential of CRISPR technology and its ability to transform healthcare as we know it
5. (2019) CRISPR: The story of us | TED Institute - For nearly a century, scientists have been studying the human genome to better understand what makes us, us.
6. (2022) Imagining CRISPR Cures | Fyodor Urnov | TEDxBerkeley - Fyodor Urnov explores the future of CRISPR and how it has the potential to save lives.

?? Humor and Pop Culture

• The Simpsons S:25 Ep. 13 The Man Who Grew Too Much - When Lisa protests against genetically-modified foods, she discovers that the town's newest chemical engineering plant is owned by Sideshow Bob, who's using the plant and the position to genetically modify himself.
• The Big Bang Theory: The Recombination Hypothesis – An episode featuring a humorous take on genetic editing.
• RISPR-Cas9 ("Mr. Sandman" Parody) | A Capella Science

?? Science Fiction

• Orphan Black (2013-2017) - This series revolves around a woman who discovers she is one of several clones, which leads her into a deep conspiracy involving genetic experimentation and ethical dilemmas. Orphan Black on IMDb
• Altered Carbon (2018-2020) - Set in a future where consciousness can be transferred between bodies, exploring themes of identity and the impact of technology on human experience. Altered Carbon on IMDb
• "Gattaca" (1997): Gattaca on IMDb - This film explores a future where genetic engineering determines social status, delving into themes of genetic determinism and personal aspiration.
• "Blade Runner 2049" (2017): Blade Runner 2049 on IMDb - Set in a dystopian future, the film examines genetic engineering, identity, and the essence of humanity, focusing on the implications of creating and manipulating artificial beings.

Subcategories and Resources in Biotechnology and Gene Editing

?? Gene Therapy

• Spark Therapeutics - Known for their work in gene therapy to treat inherited genetic disorders.
• Bluebird Bio - Focuses on developing gene therapies for severe genetic diseases and cancer.

?? Synthetic Biology

• Ginkgo Bioworks - Designs custom microbes for customers across multiple markets.
• Synthego - Provides engineered cells and CRISPR kits to facilitate genetic research and application.

?? Agricultural Biotechnology

• Benson Hill Biosystems - Uses CRISPR and other technologies to improve crop performance.
• Calyxt - Focuses on healthier food ingredients through gene editing.

About My Experience with CRISPR

I first became interested in gene editing after watching Star Trek: The Next Generation. I discovered CRISPR from a TED talk by Jennifer Doudna in 2015.

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Sources Cited

Choi, B., Yu, X., Castano, A., Darr, H., Henderson, D., Bouffard, A., Larson, R., Scarfò, I., Bailey, S., Gerhard, G., Frigault, M., Leick, M., Schmidts, A., Sagert, J., Curry, W., Carter, B., & Maus, M. (2019). CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. Journal for Immunotherapy of Cancer, 7. https://doi.org/10.1186/s40425-019-0806-7.

Dever, D., & Porteus, M. (2016). Beta-Globin Gene Targeting in Human Hematopoietic Stem Cells Using Cas9 Ribonucleoprotein and rAAV6. Blood, 128, 2310-2310. https://doi.org/10.1182/BLOOD.V128.22.2310.2310.

Kang, H., Minder, P., Park, M., Mesquitta, W., Torbett, B., & Slukvin, I. (2015). CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.. Molecular therapy. Nucleic acids, 4, e268 . https://doi.org/10.1038/mtna.2015.42.?

Lin, M., Paik, E., Mishra, B., Burkhardt, D., Kernytsky, A., Pettiglio, M., Chen, Y., Tomkinson, K., Woo, A., Cortes, M., Tan, S., Borland, T., Klein, L., Yen, A., Mahajan, S., Chan, E., Eustace, B., Porteus, M., Chakraborty, T., Cowan, C., Novak, R., & Lundberg, A. (2017). CRISPR/Cas9 Genome Editing to Treat Sickle Cell Disease and B-Thalassemia: Re-Creating Genetic Variants to Upregulate Fetal Hemoglobin Appear Well-Tolerated, Effective and Durable.. Blood, 130, 284-284. https://doi.org/10.1182/BLOOD.V130.SUPPL_1.284.284.

Maeder, M., Stefanidakis, M., Wilson, C., Baral, R., Barrera, L., Bounoutas, G., Bumcrot, D., Chao, H., Ciulla, D., DaSilva, J., Dass, A., Dhanapal, V., Fennell, T., Friedland, A., Giannoukos, G., Gloskowski, S., Glucksmann, A., Gotta, G., Jayaram, H., Haskett, S., Hopkins, B., Horng, J., Joshi, S., Marco, E., Mepani, R., Reyon, D., Ta, T., Tabbaa, D., Samuelsson, S., Shen, S., Skor, M., Stetkiewicz, P., Wang, T., Yudkoff, C., Myer, V., Albright, C., & Jiang, H. (2019). Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nature Medicine, 25, 229 - 233. https://doi.org/10.1038/s41591-018-0327-9.

Min, Y., Bassel-Duby, R., & Olson, E. (2019). CRISPR Correction of Duchenne Muscular Dystrophy.. Annual review of medicine, 70, 239-255 . https://doi.org/10.1146/annurev-med-081117-010451.

Suzuki, S., Crane, A., Anirudhan, V., Barillà, C., Matthias, N., Randell, S., Rab, A., Sorscher, E., Kerschner, J., Yin, S., Harris, A., Mendel, M., Kim, K., Zhang, L., Conway, A., & Davis, B. (2020). Highly Efficient Gene Editing of Cystic Fibrosis Patient-Derived Airway Basal Cells Results in Functional CFTR Correction.. Molecular therapy : the journal of the American Society of Gene Therapy. https://doi.org/10.1016/j.ymthe.2020.04.021.

Wang, D., Prager, B., Gimple, R., Aguilar, B., Alizadeh, D., Tang, H., Lv, D., Starr, R., Brito, A., Wu, Q., Kim, L., Qiu, Z., Lin, P., Lorenzini, M., Badie, B., Forman, S., Xie, Q., Brown, C., & Rich, J. (2020). CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies.. Cancer discovery. https://doi.org/10.1158/2159-8290.cd-20-1243.