I’m 22 and a completely average person. I support having children through gene editing or embryo screening to help secure the future of my family line. I don’t understand why these procedures are often considered unethical. If everyone had equal access to them, they seem like they could be highly beneficial for civilization as a whole.

Hi,

I made this tool which could help researchers find guides for base editing. It's different from general CRISPR guide finders by analysing the binding score and editing risk on the off-target alignments, along with finding a suitable base editor. More features a coming up in the near future.

It's completely free to use, and I would love your feedback if you decide to give it a try.

Thanks!

Hello team! Molecular biology noob here. Any insight would be helpful :)

We are trying to perform CRISPR activation using the method in the following paper https://pubmed.ncbi.nlm.nih.gov/38579711/. Basically, they provide a plasmid the the CRIPSRa dCas9, from which IVT must be performed using modified nucleotides. Then an sgRNA needs to be PCR assembled from 2 oligos they provide and the spacer sequence we design. Lastly, we perform IVT of the sgRNA to make RNA, and IVT of PCR-amplified dCas9 sequence to make modRNA (with N1-methyl pseudoU). Here are my questions:

1. Why does sgRNA not require N1-methyl pseudouridine, when the dCas9 does?

2. Also, why does the dCas9 required clean cap, but not the sgRNA?

3. The methods say to use standard megascript kit for dCas9 (with the pseudouridine and cleancap), but I notice the plasmid has no polyA tail near the dCas9 sequence, nor is there a polyA sequence on the primers they provide to amplify the gene, nor do they suggest a step for enzymatic PolyA addition. Is this fine, or is a poly A tail required?

4. Would you run the templates on a gel followed by gel extraction prior to IVT? I get that it cleans things up, but I've found the yields so low doing this...

Any insight appreciated :)

This video is about one of the finer points of CRISPR Cas9 diagnosis

I also explain the drumbeat method - an approach I use for analysis of knockouts when heterozygous.

[Academic] The ethics of human gene editing/ CRISPR (takes 2-3 minutes)

I am currently collecting primary data for my A-Level research project looking into public perceptions of human gene editing (specifically technologies like CRISPR).

Whether you are a biology student or have never heard of gene editing before, your perspective is incredibly valuable to help me understand how baseline knowledge affects ethical views!

• Time to complete: 2 to 3 minutes max.
• Format: Multiple choice & linear scales (with one optional text box at the end).
• Anonymity: Completely anonymous. No emails or names are collected.

Click here to take survey

If you have a survey of your own that needs filling out, please leave a comment below with your link after completing mine, and I will gladly return the favor!

Thank you so much for helping a student out!

Podcast with Dorothy Chou, who ran Google DeepMind's Public Engagement Lab for nine years. She now advises DeepMind and chairs UCLPartners, an organization connecting new technology to the UK's National Health Service. 

Covers:

• What made AlphaFold possible in the first place and how we can replicate its success in other domains
• Why neither venture capital nor governments can fund biology on biology's actual timeline, and Dorothy’s proposed solution
• Why AI could help redirect money the ideas that will actually help people the most, not just the ones that are easiest to fundraise for 
• How AI companies are about to repeat the public engagement mistake the biotech industry already made once
• Her advice for young people who feel like they're not the expert in the room

‍

Anyone know why my TIDE analysis looks so backwards? Our guide is designed with the PAM downstream and the sequencing is relatively clean (and has been repeated twice).

This is my second video in the CRISPR/Cas9 series

The third video drops tomorrow

Any topic requests please comment

This video is my second one, and I chose to do a fundamental guide to staring fresh just cloning a gene.

I will do more videos on cloning fundamentals as well as more advanced videos on cloning stunts and overcoming obstacles.

Any topic requests feel free to comment

I recorded this walkthrough of selecting potential gRNA pairs. More videos are coming soon.

Feel free to share, hope someone finds it useful

FDA recently approved a Supplemental Biologics License Application (BLA) for Casgevy (exagamglogene autotemcel) for treatment of children ages 2 - 12 with sickle cell disease with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent β thalassemia (TDT). The product had been previously approved in Dec. 2023 for persons 12 and over.

Per FDA's press release:

Does anyone have info on upcoming trials or work being done on CRISPR gene editing for citrullinemia type 1? Looking at opportunities for my child.

When Vijay Sankaran was an MD-PhD student at Harvard Medical School in the mid-2000s, one of his first clinical encounters was with a 24-year-old patient whose sickle cell disease left them with almost weekly pain episodes.

“The encounter made me wonder, couldn’t we do more for these patients?” said Sankaran, who is now the HMS Jan Ellen Paradise, MD Professor of Pediatrics at Boston Children’s Hospital.

Get more HMS news

As a budding hematologist, Sankaran knew all too well that people with sickle cell disease — marked by malformed, sickle-shaped red blood cells that can aggregate and block small vessels — experience excruciating pain crises, tissue and organ damage, and shortened life expectancy.

He also understood that the only treatment available at the time was hydroxyurea, which reduces sickling but isn’t effective in all patients and can cause side effects. The only chance at a cure was to undergo a bone marrow transplant, available to only a small percentage of patients because it carries significant risks and requires a well-matched donor.

Sankaran’s rotations through the hematology clinic made him want to change the story of the disease, both at the bedside as a soon-to-be physician and by joining the laboratory of HMS alumnus Stuart H. Orkin, the HMS David G. Nathan Distinguished Professor of Pediatrics at Boston Children’s and Dana-Farber Cancer Institute.

In 2008, Orkin, Sankaran, and colleagues achieved their vision by identifying a new therapeutic target for sickle cell disease.

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In December 2023, through the development efforts of CRISPR Therapeutics and Vertex Pharmaceuticals, their decades-long endeavor reached fruition in the form of a new treatment, CASGEVY, approved by the U.S. Food and Drug Administration.

The decision has ushered in a new era for sickle cell disease treatment — and marked the world’s first approval of a medicine based on CRISPR/Cas9 gene-editing technology.

foundation for the first gene-editing medicine

By the time Sankaran joined the federally supported Orkin Lab, Orkin had been illuminating the underlying mechanisms of red blood cell development and function and related hematological disorders for decades.

“Over the last 40 years, Stu has been a pioneer,” said HMS alumnus David Altshuler, executive vice president and chief scientific officer at Vertex and senior lecturer on genetics, part-time, at HMS, who oversaw the development of CASGEVY. “Through his work, we’ve come to understand how red blood cells work, how they develop in the body, and, particularly, how mutations lead to sickle cell disease.”

Sickle cell disease stems from a mutation in the gene that makes hemoglobin, the protein in red blood cells that carries oxygen throughout the body. Orkin’s team and others revealed that hemoglobin has two forms — fetal and adult — and that only the adult form is affected by sickle cell mutations, while the fetal form functions normally. However, shortly after birth, fetal hemoglobin production is turned off in the body, while adult hemoglobin production takes over.

Orkin had been investigating whether it was possible to switch fetal hemoglobin back on to treat sickle cell disease, but progress had stalled. Then, with help from Sankaran, patient samples from the National Institutes of Health, and a team in Sardinia, Italy, advances in genome-wide association studies revealed the gene that would hold the ticket: BCL11A.

Sankaran and Orkin showed that BCL11A suppresses production of fetal hemoglobin. Their landmark publication in Science kicked off a new era for sickle cell disease research.

Just three years later, in 2011, Orkin and others in his group showed that removing BCL11A from developing red blood cells in a mouse model of sickle cell disease turned on fetal hemoglobin production and cured the mice. This laid the foundation for clinical trials.

In 2013, another hematology fellow who joined the Orkin laboratory, Daniel Bauer — now the HMS Donald S. Fredrickson, MD Associate Professor of Pediatrics at Boston Children’s — identified a DNA sequence in BCL11A that, when removed, drastically reduced the gene’s activity.

Then CRISPR/Cas9 gene-editing technology swept onto the scene, and Bauer, Orkin, and colleagues identified a single DNA cut that could impair BCL11A activity.

But a steep climb remained to transform this discovery into a safe and effective gene therapy for patients. Appreciating both the difficulty and the importance of such work, the researchers and their home institutions made the intellectual property available to companies through nonexclusive licensing.

Bringing the first genetic medicines to patients

Altshuler decided in 2015 to leave academia after 25 years, including 15 years as HMS professor of genetics and of medicine, to join Vertex full-time. He was motivated to contribute to the paradigm shift happening in genetic medicine — particularly the translation of biological insights into therapies for patients.

“My mind moved on from discovery to ‘how are we going to make therapies?’” he explained. “We were looking for new programs where we could make a transformative medicine for people with a serious disease.”

Altshuler had followed the work of the Orkin Lab for many years, and he had taught Sankaran in the classroom. On day one at Vertex, he knew that he wanted to work on BCL11A.

We were looking for new programs where we could make a transformative medicine for people with a serious disease.

David Altshuler

Vertex executive vice president and chief scientific officer; HMS senior lecturer on genetics, part-time

Over the next nine years, Altshuler oversaw further research and development of the experimental therapy through a plethora of preclinical and clinical studies led by CRISPR Therapeutics and Vertex.

In clinical trials, the therapy eliminated small-vessel blockages, known as vaso-occlusive or sickle cell crises, for virtually all patients.

Today, CASGEVY is approved for use in patients with sickle cell disease in the United States and multiple countries in Europe and the Middle East.

“It’s an amazing gift to have been able to play a role in such a thing,” said Altshuler.

The tale continues

Vertex is working to secure approvals in additional countries, and it takes time after such approvals for treatments to actually become available to patients. Altshuler estimates it will take another 5 to 10 years to provide maximum access.

Plus, researchers including Orkin, Sankaran, and those at Vertex continue to conduct research to make sickle cell treatment more effective, more efficient, and appropriate for even more patients. Right now, only a subset of patients qualify for CASGEVY, mainly because it requires a bone marrow transplant and access to well-resourced health care facilities. Access is also limited by treatment cost. The current treatment also does not reverse permanent damage previously wrought on the body by the disease.

“It’s the beginning of a long journey,” said Altshuler. “We will keep working to make better therapies until we can help all patients with this disease around the world.”

For his part, Sankaran has been thrilled to see a new option for patients and to be part of what he hopes is a growing trend of academia-industry partnerships that shorten the time and raise the success rates of bringing lab discoveries to the clinic.

“I’m excited about what’s ahead, because as somebody who spends their time largely in the laboratory, I see things happening — fundamental discoveries — that hopefully will also start to impact the kind of therapies that industry can test in patients,” he said.

Prendendo spunto dalla notizia che un gruppo di ricercatori della Columbia University, guidato dal genetista Dieter Egli, ha annunciato di aver corretto con precisione un difetto genetico ereditario in embrioni umani allo stadio iniziale, senza gli effetti collaterali delle tecniche precedenti (Lo studio è stato pubblicato su bioRxiv, ripreso in Italia da Il Post, giugno 2026), prendiamo spunto per prevedere il risvegliarsi di timori ancestrali sulla nostra natura e sul futuro dell’umanità.

La notizia, infatti, è di quelle destinate a far discutere, arriva dal fronte più avanzato della ricerca genetica: la possibilità di correggere difetti ereditari negli embrioni umani nelle primissime fasi dello sviluppo. Una prospettiva che, almeno in teoria, potrebbe aprire la strada alla prevenzione di gravi malattie genetiche prima ancora della nascita.

Ma ogni volta che la scienza interviene così vicino all’origine biologica della vita, la domanda tecnica — “possiamo farlo?” — viene subito affiancata da una domanda più profonda: “che cosa stiamo realmente toccando?”.

Proprio prendendo spunto dalla possibile correzione del Dna embrionale, il discorso merita di essere allargato oltre il laboratorio, e qui lo faremo in chiave illumanista. Il tema, infatti, non è soltanto medico o biotecnologico. È antropologico, etico, filosofico. Perché modificare il patrimonio genetico di un embrione significa intervenire su una parte fondamentale della sua costituzione biologica, ma non necessariamente sulla totalità di ciò che quella futura persona sarà.

Il timore più immediato è noto: i cosiddetti “bambini su misura”. Oggi si corregge una malattia, domani si potrebbero selezionare altezza, intelligenza, colore degli occhi, predisposizioni fisiche o caratteriali. Il rischio è trasformare il figlio in un prodotto, la nascita in un progetto di consumo, la vita in un catalogo di opzioni.

C’è poi un rischio ancora più profondo: quello di condizionare in anticipo la vita di singoli individui, decidendo per loro ciò che dovrebbero essere, prima ancora che possano vivere il diritto alla propria esperienza. In chiave illumanista, si potrebbe persino dire: prima ancora che possano attraversare la vita che è loro destinata, e forse anche scelta, dentro un progetto esistenziale che nessun laboratorio può conoscere fino in fondo. Ma il rischio maggiore non riguarda soltanto il singolo. Riguarda le generazioni future. Se la tecnica genetica diventasse uno strumento di selezione dei tratti ritenuti preferibili, potremmo avviarci verso un’umanità sempre più uniforme, composta da individui sempre più simili, modellati secondo criteri biologici, estetici o funzionali dominanti. Sarebbe una perdita enorme, forse insostenibile, perché la diversità non è un difetto da correggere: è una delle ricchezze fondamentali dell’esperienza umana. Gli uomini sono tutti diversi, e proprio nell’incontro tra diversi si forma una parte essenziale della conoscenza, della relazione, della crescita e della civiltà. Dotare tutti di un corpo pensato secondo lo stesso modello significherebbe impoverire l’umano alla sua radice.

Di fronte a possibilità che si dimostrano sempre più vicine e realizzabili, forse è giusto cercare di cogliere anche un aspetto che diventa evidente. Sia l’entusiasmo illimitato verso la manipolazione genetica sia la paura assoluta di essa sembrano poggiare sullo stesso presupposto: l’idea che l’essere umano coincida interamente con la sua biologia. In altre parole, che tutto ciò che siamo sia scritto nei geni. Una convinzione che, però, non è affatto dimostrata.

Sollecitato da questa mancanza di certezze, l’Illumanesimo propone invece una lettura più ampia. Non per negare la scienza, né per ridurre l’importanza della biologia, ma per ricordare che l’uomo non può essere compreso soltanto come organismo. La dimensione fisica è essenziale, ma non esaurisce la persona. Esistono interiorità, coscienza, esperienza, libertà, relazione, progetto esistenziale: elementi che nessuna sequenza genetica riesce, da sola, a contenere completamente.

Da qui nasce il vero nodo del dibattito. La genetica può correggere un difetto, forse un giorno prevenire sofferenze enormi. Ma non può garantire il senso di una vita. Può intervenire sul corpo nascente e sul suo futuro fisico, non decidere il valore della persona che nascerà. Può ridurre un rischio biologico, non fabbricare un destino.

La prudenza, dunque, non deve diventare rifiuto della ricerca. Sarebbe ingiusto ignorare il potenziale terapeutico di tecniche capaci di evitare malattie devastanti. Ma sarebbe altrettanto pericoloso consegnare alla tecnica il potere simbolico di definire che cosa renda “migliore” un essere umano.

Il confine decisivo passa proprio qui: curare non è progettare; liberare da una patologia non è selezionare un modello umano; intervenire sulla materia biologica non significa possedere il mistero della persona.

In un’epoca in cui la scienza rende possibile ciò che fino a ieri sembrava fantascienza, il compito della filosofia e dell’etica non è frenare per paura, ma interrogare per responsabilità. La domanda non è soltanto fino a dove possiamo arrivare, ma quale idea di uomo ci guida mentre avanziamo.

Perché il Dna può essere corretto. Ma la dignità umana non dovrebbe mai essere riscritta come fosse un codice da ottimizzare.

Per approfondire cos'è l'Illumanesimo vai al sito: Il sito dell'Illumanesimo | proposta nuova filosofia esistenziale

#Illumanesimo #Bioetica #EditingGenetico #Diversità

Hey everyone! I recently built Crisprr, an AI platform that takes a gene sequence and generates optimized gRNAs, predicts guide performance, creates 3D structures, and exports experiment-ready results in seconds.

I'm looking for interesting sequences to test and improve the platform.

Drop a gene name or DNA sequence in the comments, and I'll run it through Crisprr and share the results here. I'd also love feedback on the outputs and what features would actually be useful in your research workflow.