UCLA opens Center for Advanced Biotherapies, expanding capacity to develop and deliver personalized cell and gene therapies

Good news!

"Key takeaways 

• UCLA has opened the Center for Advanced Biotherapies, a 14,000-square-foot FDA-compliant manufacturing facility that nearly doubles the institution’s capacity to produce cell and gene therapies for patients enrolled in clinical trials.
• The facility — built with support from the National Institutes of Health and the California Institute for Regenerative Medicine — is equipped to manufacture a broad range of personalized treatments, from cancer vaccines to stem cell gene therapies.
• The facility’s proximity to UCLA’s hospitals and clinics means researchers can move a therapy from the manufacturing suite to an early phase clinical trial patient’s bedside the same day.

For 30 years, the UCLA Human Gene and Cell Therapy Facility has been the quiet engine behind some of the university’s most ambitious clinical research, supporting more than 25 clinical trials and producing over 300 personalized therapy products for patients with cancer, HIV/AIDS, sickle cell disease and rare genetic disorders. But the science consistently exceeded what the space was designed for. ...

The center features 10 cleanrooms, including seven manufacturing suites designed to run multiple therapies simultaneously, two bioengineering rooms built for large-scale equipment, including bioreactors and 3D printers, and a dedicated suite for viral vector manufacturing. A centralized quality control laboratory supports comprehensive product testing and release.  ..."

UCLA opens Center for Advanced Biotherapies, expanding capacity to develop and deliver cell and gene therapies | UCLA

Three researchers in full white protective suits and gloves work inside a sterile cleanroom laboratory, viewed through a glass door.

CRISPR takes a bold leap toward silencing Down syndrome's extra chromosome

Good news!

P.S. Google Scholar and Semantic Scholar (see screen print below) do not yet list this research paper published on 4/13/2026 as of writing this blog. This paper was published in the prestigious PNAS!

"Scientists have taken an important step toward a gene therapy that could one day turn off the extra genetic material that causes Down syndrome (DS). Down syndrome is a genetic condition caused by an extra chromosome 21 (and consequently hundreds of triplicate genes) that leads to developmental and neurological issues. ...

The team used a modified version of the gene-editing technique CRISPR/Cas9 ...  to insert the XIST gene into the extra chromosome 21 to silence it.

They tested their technique in the lab using human stem cells that contained an extra chromosome 21. After running several experiments, the team found that CRISPR was effective at pasting the XIST silencing gene exactly where it needed to go. ..."

From the highlights and abstract:

"Significance

Down syndrome (DS) results from trisomy 21 and remains without a molecularly targeted therapy. 

Prior work demonstrated that ectopic expression of the long noncoding RNA XIST could epigenetically silence the extra chromosome 21, but technical limitations, including low gene integration efficiency, have hindered translational progress.

Here, we present a CRISPR-based approach that markedly improves the efficiency and specificity of XIST integration into an extra copy of chromosome 21. By engineering Cas9-exonuclease fusion, designing SNP-specific sgRNAs, and enhancing donor–acceptor DNA pairing, we achieve a significant improvement in silencing efficiency. Our findings demonstrate partial transcriptional correction of trisomic gene dosage and offer a scalable, targeted platform for chromosomal therapy in DS and other aneuploidies.

Abstract

Down syndrome (DS) is one of the most common developmental human genetic disorders and is due to triplication of chromosome 21 (HSA21).

Although previous studies using epigenetic suppression of HSA21 by the long noncoding RNA XIST showed a potential for DS treatment, integration efficiency of XIST by conventional zinc finger nucleases is too low to allow for practical implementation.

Here, we report a modified CRISPR/Cas9 approach, which enhances the efficiency of XIST gene integration.

First, a codon-optimized λ-phage exonuclease (exo) was fused with Cas9 to create 5’- and 3’-end overhangs at cutting sites of donor DNA and acceptor chromosome DNA.

Second, four sgRNAs, two of which selectively targeted each the acceptor or donor DNA, were assembled tandemly into one Cas9 plasmid (PX459) to increase the Cas9-cutting efficiency and promote donor DNA integration.

Third, sgRNAs were designed by searching for unique single nucleotide polymorphism nucleotides distinct between the three HSA21 copies, as a protospacer adjacent motif site to specifically target one HSA21 copy.

Fourth, donor DNA plasmid containing XIST was modified to disable replication and inhibit transcription function and allow for inducible expression.

Our modified CRISPR method significantly enhanced the integration efficiency (20 to 40%) of long XIST gene (14 kb) into an extra chromosome 21 (HSA21), as was identified with PCR, cell cloning, immunostaining, and FISH.

RNA sequencing results showed that imbalance of gene transcription across extra HSA21 can be partially corrected by XIST gene integration. The modified CRISPR method with XIST paves a road for therapeutic treatment for DS."

CRISPR takes a bold leap toward silencing Down syndrome's extra chromosome

A modified CRISPR/Cas9 approach in silencing the triplication in Down syndrome: A treatment path XISTs (no public access)

Gene editing shown to correct rare brain mutations in mice

Amazing stuff! This is just the beginning!

"Scientists have used a single injection to correct gene mutations caused by an ultra-rare disease, improving symptoms and survival rates in mice.

Published in Cell, the gene editing study targeted the 2 most common mutations that cause alternating hemiplegia in childhood (AHC). ..."

"... The new study ... is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. Prime editing was developed in 2019  ... The technology has already been successfully tested in a clinical trial for another rare genetic disease. ..."

From the highlights and abstract:

"Highlights

• Prime editing and base editing efficiently correct ATP1A3 mutations in AHC patient cells

• AAV9-delivered prime editing restores Atp1a3 sequence and ATPase function in mice

• In vivo prime editing also strongly rescues behavioral phenotypes and extends lifespan

• Prime editing can serve as a one-time treatment to rescue a neurological disorder

Summary

Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disorder with no disease-modifying treatment. Mutations in ATP1A3, encoding an Na+/K+ ATPase subunit, cause 70% of AHC cases.

Here, we present prime editing (PE) and base editing (BE) strategies to correct ATP1A3 and Atp1a3 mutations in human cells and in two AHC mouse models.

We used PE and BE to correct five prevalent ATP1A3 mutations with 43%–90% efficiency. AAV9-mediated in vivo PE corrects Atp1a3 D801N and E815K in the CNS of two AHC mouse models, yielding up to 48% DNA correction and 73% mRNA correction in bulk brain cortex.

In vivo PE rescued clinically relevant phenotypes, including restoration of ATPase activity; amelioration of paroxysmal spells, motor defects, and cognition deficits; and dramatic extension of animal lifespan.

This work suggests a potential one-time PE treatment for AHC and establishes the ability of PE to rescue a neurological disease in animals."

Gene editing shown to correct rare brain mutations in mice

Prime editing treats childhood brain disease in mice (original news release) "Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy."

Mouse models for ultra-rare disorder could pave the way for nervous system gene editing therapies (original news release) "The models offer clear insights into how alternating hemiplegia of childhood progresses—and how it might be stopped"

In vivo prime editing rescues alternating hemiplegia of childhood in mice (open access)

Graphical abstract

Gene therapy shows promise for reversing heart failure

Good news!

"... The new gene therapy ... prevented heart failure (HF) from worsening and even improved some key measures of heart function in pig models. ..."

"A new gene therapy can reverse the effects of heart failure and restore heart function in a large animal model, according to new research ... The therapy increases the amount of blood the heart can pump and dramatically improves survival, in what the study calls “an unprecedented recovery of cardiac function.”

Currently, heart failure is irreversible. In the absence of a heart transplant, most medical treatments aim to reduce the stress on the heart and slow the progression of the often-deadly disease. But if the gene therapy shows similar results in future clinical trials, it could help heal the hearts of the one in four people alive today who will eventually develop heart failure. ..."

From the abstract:

"Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice.

Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter. Using a minipig model of right ventricular tachypacing-induced non-ischemic dilated cardiomyopathy and chronic HFrEF, we identified that a single intravenous low dose (6 × 1011 vg/kg) of adeno associated virus 9 (AAV9)-packaged cBIN1 improves ventricular remodeling and performance, reduces pulmonary and systemic fluid retention, and increases survival in HFrEF minipigs. In cardiomyocytes, AAV9-cBIN1 restores t-tubule organization and ultrastructure in failing cardiomyocytes. In conclusion, AAV9-based cBIN1 gene therapy rescues non-ischemic HFrEF with reduced mortality in minipigs."

Gene therapy shows promise for reversing heart failure

New gene therapy reverses heart failure in large animal model (original news release)

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs (open access)

Fig. 2: AAV9 transduced cBIN1 in myocardium rescues survival rates in minipigs with RVP-induced non-ischemic HFrEF.

New gene delivery vehicle shows promise for human brain gene therapy

Good news!

"In an important step toward more effective gene therapies for brain diseases, researchers ... have engineered a gene-delivery vehicle that uses a human protein to efficiently cross the blood-brain barrier and deliver a disease-relevant gene to the brain in mice expressing the human protein. Because the vehicle binds to a well-studied protein in the blood-brain barrier, the scientists say it has a good chance at working in patients.
Gene therapy could potentially treat a range of severe genetic brain disorders, which currently have no cures and few treatment options. But FDA-approved forms of the most commonly used vehicle for packaging and delivering these therapies to target cells, adeno-associated viruses (AAVs), aren’t able to efficiently cross the blood-brain barrier at high levels and deliver therapeutic cargo. ..."

From the abstract:

"Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40–50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson’s disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy."

New gene delivery vehicle shows promise for human brain gene therapy | Broad Institute Scientists have engineered an adeno-associated virus (AAV) that efficiently crosses the blood-brain barrier in human cell models and delivers genes throughout the brain in humanized mice.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery (no public access)

Brain vasculature (in blue) surrounded by RNA (in orange) transcribed from the gene delivered to the brain in humanized mice using an engineered AAV targeting the human transferrin receptor.

Pioneering gene therapy restores deaf toddler's hearing

Good news! This is only the beginning of gene therapy!

Gene-therapy breakthrough allows congenitally deaf children to hear and respond to speech in China

Good news! "may yield other treatments for more of the 30 million kids with genetic hearing loss"

"A novel gene therapy approach has given five children who were born deaf the ability to hear. The method, which overcomes a roadblock presented by large genes, may be useful in other treatments, according to researchers. ...

treated six children aged 1 to 7 who were suffering from an inherited mutation of the OTOF gene, which manufactures a protein important in transmitting signals from the ear to the brain.

Five of the six children showed improvement in hearing over the 26-week trial, with four outcomes described by researchers as “robust.” ...

The three older children, with cochlear implants turned off, could understand and respond to speech by 26 weeks, with two able to recognize speech in a noisy room and have a telephone conversation. ...

Before the trial began, researchers had to tackle a significant technical problem related to the size of the OTOF gene. The procedure called for the gene to be inserted into the cochlea using a type of virus researchers commonly use for this purpose.

The virus inserts the gene into the DNA of target cells, which then begin to manufacture the missing protein. The problem in this case is that the OTOF gene is too big for the virus to hold. Researchers got past this by dividing the gene into two, encapsulating the halves into separate viruses, and then injecting a mixture with both halves of the gene into the cochlea. ..."

"... the researchers found the novel gene therapy to be an effective treatment for patients with a specific form of autosomal recessive deafness caused by mutations of the OTOF (otoferlin) gene, called DFNB9. With its first patient treated in December 2022, this research represents the first human clinical trial to administer gene therapy for treating this condition ..."

From the abstract:

"Background

Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Methods

This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.

Findings

Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.

Interpretation

AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. ..."

Gene-therapy breakthrough allows congenitally deaf children to hear — Harvard Gazette Harvard scientist co-leads research, which targeted specific condition, may yield other treatments for more of the 30 million kids with genetic hearing loss

Gene Therapy Restores Hearing in Children with Hereditary Deafness

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial (no public access)

Deaf since birth, some children in China can hear after gene treatment

Good news! Sometimes miracles do happen!

"... But this year her family, who live in a high-rise block in the city of Dongguan, enrolled her in a study of a new type of gene therapy. During the procedure, doctors used a virus to add replacement DNA to the cells in Yiyi’s inner ear that pick up vibrations, allowing them to transmit sound to her brain.

In less than a month, her mother says, she was hearing with the treated ear for the first time. ...
The feat is even more remarkable because until now, no drug of any kind has ever been able to improve hearing. ...
Otoferlin gene defects are the cause of around 1% to  3% of cases of inborn deafness, and there are only about 900 new cases a year in China, meaning the condition is rare. ...

The new treatment is designed to add a working copy of the otoferlin gene. Because of the gene’s large size—it is around 6,000 DNA letters long—it had to be broken into two parts, each packaged separately into millions of copies of a harmless virus. ... then carefully injects the loaded viruses deep into a fluid-filled chamber in a part of the children’s ears called the cochlea. ...

the children’s hearing improved, on average, from not hearing anything under 95 decibels (as loud as a motorcycle) to hearing sounds at 50 to 55 decibels—about the level of a regular conversation.

“They reach maybe 60% to 65% of normal hearing,” ..."

Deaf since birth, some children in China can hear after gene treatment | MIT Technology Review After gene therapy, Yiyi can hear her mother and dance to the music. But why is it so noisy at night?

Study shows promise of gene therapy for alcohol use disorder with dramatic results

Good news!

"... The study in nonhuman primates showed that implanting a specific type of molecule that induces cell growth effectively resets the brain’s dopamine reward pathway in animals predisposed to heavy drinking. The gene therapy procedure involves brain surgery, and may be useful in the most severe cases of alcohol use disorder. ...

The implanted virus is not harmful and carries a gene that codes for the protein known as glial-derived neurotrophic factor, or GDNF. It was injected in a specific area of the brain of a group of rhesus macaque monkeys that voluntarily and heavily drink ethanol diluted in water.  After four macaques underwent the procedure, researchers found their consumption dropped by more than 90% compared with a control group. ...

Veterinarians at the ONPRC used magnetic resonance imaging to guide the insertion of GDNF, using an adeno-associated virus in the ventral tegmental area of the brain. The adeno-associated virus is a single-stranded DNA virus that does not cause disease in its subject. The procedure is already used in adult patients with Parkinson’s disease and in children to treat a rare genetic disorder known as aromatic L-amino acid decarboxylase deficiency that, among other symptoms, causes difficulty with movement. ..."

From the abstract:

"Alcohol use disorder (AUD) exacts enormous personal, social and economic costs globally. Return to alcohol use in treatment-seeking patients with AUD is common, engendered by a cycle of repeated abstinence-relapse episodes even with use of currently available pharmacotherapies. Repeated ethanol use induces dopaminergic signaling neuroadaptations in ventral tegmental area (VTA) neurons of the mesolimbic reward pathway, and sustained dysfunction of reward circuitry is associated with return to drinking behavior. We tested this hypothesis by infusing adeno-associated virus serotype 2 vector encoding human glial-derived neurotrophic factor (AAV2-hGDNF), a growth factor that enhances dopaminergic neuron function, into the VTA of four male rhesus monkeys, with another four receiving vehicle, following induction of chronic alcohol drinking. GDNF expression ablated the return to alcohol drinking behavior over a 12-month period of repeated abstinence–alcohol reintroduction challenges. This behavioral change was accompanied by neurophysiological modulations to dopamine signaling in the nucleus accumbens that countered the hypodopaminergic signaling state associated with chronic alcohol use, indicative of a therapeutic modulation of limbic circuits countering the effects of alcohol. These preclinical findings suggest gene therapy targeting relapse prevention may be a potential therapeutic strategy for AUD."

Study shows promise of gene therapy for alcohol use disorder | OHSU News Already used to treat Parkinson’s disease, OHSU researchers found surgical treatment dramatically reduced chronic heavy drinking

GDNF gene therapy for alcohol use disorder in male non-human primates (no public access)

Fig. 2: AAV2-hGDNF delivery to the VTA.

Delivering Gene Therapies in Utero to treat genetic skin diseases

Good news! Amazing stuff! This is still rather preliminary work (I was not able to find the research paper).

"... One example is epidermolysis bullosa, which causes the skin to blister and break, leaving gaping, slow-healing wounds. ... researchers presented preliminary work suggesting that lipid nanoparticles could one day deliver mRNA-based gene therapies to treat skin diseases in utero.  ...

By injecting lipid nanoparticles directly into the amniotic fluid of pregnant mice, the researchers successfully delivered mRNA molecules to fetal skin. Combined with gene editing machinery like CRISPR, the technology may one day lead to treatments for genetic skin diseases before babies are born. ..."

Delivering Gene Therapies in Utero  | The Scientist Magazine® By delivering mRNA to the skin of mice in utero, researchers showed a proof-of-concept for shuttling gene therapies to skin cells before birth.

The FDA just approved rub-on gene therapy that helps “butterfly” children

Amazing stuff! Just rub it on! This is almost like a miracle healing!

"Antonio Vento is 13 years old. He’s a tiny figure in bandages who doesn’t walk and, until recently, couldn’t see more than shadows. He has dystrophic epidermolysis bullosa, an inherited disease that makes his skin so fragile that kids with the illness are called “butterfly children.”

But now, thanks to a novel gene therapy squirted onto his skin and dripped into his eyes, things are better. His wounds have gotten smaller, and a visit to the eye doctor this week confirmed that his vision had dramatically improved. ..."

"... How it works: The treatment introduces a missing gene to skin cells so they can make collagen. It’s already helping people with dystrophic epidermolysis bullosa, a rare inherited disease that makes skin incredibly fragile. The topical ointment helps to heal the disease’s chronic, blistering wounds, while an eyedrop version can prevent scar tissue from building up in their eyeballs and improve their vision. ...

Dystrophic Epidermolysis Bullosa (DEB) is a serious rare genetic disease that affects the skin and mucosal tissues and is caused by one or more mutations in the COL7A1 gene, resulting in lack of production of functional type VII collagen (COL7) protein

VYJUVEK is a topical gel that addresses the genetic cause of DEB by restoring functional copies of the COL7A1 gene to patients and is the only medicine available for patients in the US

VYJUVEK is approved for the treatment of patients six months of age or older with either recessive or dominant DEB ..."

Krystal Biotech just got the first approved gene therapy for skin disease | MIT Technology Review Biotech companies are getting creative with how they deliver DNA fixes into people's bodies.

Krystal Biotech Receives FDA Approval for the First-Ever Redosable Gene Therapy, VYJUVEK™ (beremagene geperpavec-svdt) for the Treatment of Dystrophic Epidermolysis Bullosa

Anthony Vento with his mother and father. His skin disease is being treated with a newly approved gene therapy.

Teenager's treatment resistent, relapsed leukemia cured within one month with world's first new base editing gene therapy in the UK

Amazing stuff! Cancer is history (soon)!

"[The teenager] was diagnosed with T cell leukemia in mid-2021, and after exhausting all current therapies was on her way to palliative care. Now, six months after the experimental treatment, she is still in full remission. ...
The patient's incurable leukemia was effectively cleared using "base-edited" immune T-cells from a donor. ...
The technology behind the innovative new treatment is barely five years old, with researchers originally describing the technique as "CRISPR 2.0." Unlike prior CRISPR gene editing techniques, which act essentially like cut-and-paste tools, base editing is much more targeted and precise. ...
In this new instance, base editing was utilized to create a novel treatment for a 13-year-old patient suffering T-cell acute lymphoblastic leukemia. This incurable form of cancer involves a patient's T cells not maturing effectively and disrupting other blood cells. ...

The base edits altered several key markers that identify the immune cells as T cells. This meant the edited cells were essentially invisible to other T cells.

Other base edits to the T cells removed markers that were unique to the donor, turning the cells into a "universal" treatment. ...
Within a month of receiving the experimental therapy the patient, named Alyssa, was completely leukemia free. Now, six months later, Alyssa is still in complete remission. ...
The preliminary clinical trial is looking to enroll another 10 patients over the coming years but this leukemia treatment is just the tip of the iceberg for base editing technology. At least three other trials are already underway testing base editing to treat sickle-cell anemia, high cholesterol and a blood disorder called beta-thalassemia. ..."

"... She was treated with all current conventional therapies for her blood cancer, including chemotherapy and a bone marrow transplant, but unfortunately her disease came back and there were no further treatment options. ..."

Teenager's "incurable" leukemia cured by new base editing gene therapy

GOSH patient receives world-first treatment for her 'incurable' T-cell leukaemia

World-first use of base-edited CAR T-cells to treat resistant leukaemia

Immusoft Announces FDA Clearance of IND Application for ISP-001 for MPS I, the First Engineered B Cell Therapy to Enter into Clinical Trials

Good news! Could that be a game changer? This approach may not be limited to rare diseases. This may only be the beginning!

"Immusoft makes history with the first engineered B cell investigational therapy cleared for human trials

Immusoft seeks to improve the treatment of MPS I, a rare childhood disease, through the use of its Immune System Programming (ISP™) approach that utilizes B cells as re-dosable biofactories for therapeutic protein delivery

The company has received FDA Orphan Drug Designation and Rare Pediatric Disease Designation for ISP-001 in MPS I (Mucopolysaccharidosis type I) and will launch its Phase 1 study this year ..."

Immusoft Announces FDA Clearance of IND Application for ISP-001 for MPS I, the First Engineered B Cell Therapy to Enter into Clinical Trials - Immusoft

New Technology is One Step Closer to Targeted Gene Therapy

Good news!

"A major challenge, however, has been creating the right "delivery vehicles" that can carry genes and molecules into the cells that need treatment, while avoiding the cells that do not.

Now, a team led by Caltech researchers has developed a gene-delivery system that can specifically target brain cells while avoiding the liver. This is important because a gene therapy intended to treat a disorder in the brain, for example, could also have the side effect of creating a toxic immune response in the liver, hence the desire to find delivery vehicles that only go to their intended target. The findings were shown in both mouse and marmoset models, an important step towards translating the technology into humans. ...

The key to this technology is the use of adeno-associated viruses, or AAVs, which have long been considered promising candidates for use as delivery vehicles. Over millions of years of evolution, viruses have evolved efficient ways to gain access into human cells, and for decades researchers have been developing methods to harness viruses' Trojan-Horse-like abilities for human benefit.

AAVs are made up of two major components: an outer shell, called a capsid, that is built from proteins; and the genetic material encased inside the capsid. To use recombinant AAVs for gene therapy, researchers remove the virus's genetic material from the capsid and replace it with the desired cargo, such as a particular gene or coding information for small therapeutic molecules.

"Recombinant AAVs are stripped of the ability to replicate, which leaves a powerful tool that is biologically designed to gain entrance into cells," ... 

The shape and composition of the capsid is a critical part of how the AAV enters into a cell. Researchers in the Gradinaru lab have been working for almost a decade on engineering AAV capsids that cross the blood-brain barrier (BBB) and to develop methods to select for and against certain traits, resulting in viral vectors more specific to certain cell types within the brain. ..."

From the abstract:

"Genetic intervention is increasingly being explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies rely upon expressing a transgene in affected cells while minimizing off-target expression. Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and sequential engineering of AAV-PHP.eB between the surface-exposed AA452 and AA460 of VP3. From this selection, we identified capsid variants that were enriched in the brain and targeted away from the liver in C57BL/6J mice. This tropism extends to marmoset (Callithrix jacchus), enabling robust, non-invasive gene delivery to the marmoset brain after intravenous administration. Notably, the capsids identified result in distinct transgene expression profiles within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood–brain barrier with neuronal specificity in rodents and non-human primates enables new avenues for basic research and therapeutic possibilities unattainable with naturally occurring serotypes."

New Technology is One Step Closer to Targeted Gene Therapy | www.caltech.edu Broad and robust transgene expression across brain regions of marmoset is shown after systemic delivery with engineered capsid. Gene therapy is a powerful developing technology that has the potential to address myriad diseases. For example, Huntington's disease, a neurodegenerative disorder, is caused by a mutation in a single gene, and if researchers could go into specific cells and correct that defect, theoretically those cells could regain normal function.

AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset (open access)

A decade after gene therapy, children born with deadly immune disorder remain healthy

Good news! And this is only the beginning of realizing the enormous potential of gene therapy!

When will finally the sneeze gene be permanently removed? Probably, too late for me!

"Over a decade ago, UCLA physician-scientists began using a pioneering gene therapy they developed to treat children born with a rare and deadly immune system disorder. They now report that the effects of the therapy appear to be long-lasting, with 90% of patients who received the treatment eight to 11 years ago still disease-free.

ADA-SCID, or adenosine deaminase–deficient severe combined immunodeficiency, is caused by mutations in the gene that creates the ADA enzyme, which is essential to a functioning immune system. For babies with the disease, exposure to everyday germs can be fatal, and if untreated, most will die within the first two years of life. ..."

From the paper's abstract:

"... These patients were monitored in a long-term follow-up protocol over 8 to 11 years. Nine of 10 patients have sufficient immune reconstitution to protect against serious infections and have not needed to resume ERT or proceed to secondary allogeneic HSCT. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Four of 9 evaluable patients with the highest gene marking and B-cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. ..."

A decade after gene therapy, children born with deadly immune disorder remain healthy | UCLA UCLA researchers provide update on patients treated for ADA-SCID between 2009 and 2012

Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency

Opinion: How Biomedicine Could Transform Human Reproduction

Recommendable! Prenatal gene editing is an option that ought to be considered! The referenced article below is written by author of the MIT Press book CRISPR People: The Science and Ethics of Editing Humans.

As I wrote before, one of the first genes, if not otherwise relevant, to be permanently removed is the sneezing gene! I am sure, there are other genese, we actually do not need. As a man, I would also strongly advocate to remove the facial hair genes. Shaving is an unnecessary chore. 

I blogged her in 2019, about the possibility of an artificial womb to give birth outside of a human body. I think, it is entirely possible that in 30 years or so from now, women don't have to be pregnant and give birth anymore.

"In November 2018, the world was shocked to learn that two babies had been born in China with DNA edited while they were embryos—as dramatic a development in genetics as the 1996 cloning of Dolly the sheep."

"... Today, bad news from prenatal testing leaves would-be parents with two options: terminate the pregnancy or prepare for the birth of an ill or at-risk child. For over 30 years, parents have been able to avoid this dilemma by turning to pre-implantation genetic diagnosis (PGD). This procedure starts with in vitro fertilization (IVF), but then tests embryos before they are transferred into the uterus. ...

PGD opens yet another door. One might edit the genes of those at-risk embryos, using CRISPR or other methods, before using them to try to start a pregnancy. ...  changing the babies’ DNA in ways they could pass on to their children, because changed cells in the embryo would eventually become eggs or sperm. This argument against heritable changes would also apply when the change is made to correct disease-causing mutations—or when it is used to try to “enhance” the resulting babies. Whether such germline editing should be a “line in the sand,” not to be crossed, is hotly disputed. ...
Most of us look forward to this when it involves disease, while the (distant) prospect of “enhancement” of traits such as height or intelligence causes very mixed feelings.  ...
Now, consider that we may soon be able to make eggs and sperm from stem cells derived from a person’s skin. This technique, which has already worked in mice and is being researched with human cells, offers hope to people who cannot have their own genetic children because they lack functional sperm or eggs, as well as a potential pathway for LGBTQ couples who want to have children who are biologically their own. If the technique becomes an easy source of human eggs, it may also allow people to bypass the uncomfortable, risky, and expensive process of harvesting eggs for IVF, which could lead to a vast expansion of the use of PGD. ...
Finally, in several decades, one might be able to make a living uterus outside the body using stem cells and, by mechanically giving it blood with oxygen, nutrients, and the right hormones, use it to gestate a baby. This not-exactly-artificial womb could transform pregnancy entirely, and with it, the lives of billions of people."

Opinion: How Biomedicine Could Transform Human Reproduction | The Scientist Magazine® CRISPR and other innovations are likely to open up a wealth of new options for how people have children.

Towards The Genes Of Genius

Posted: 11/5/2019

I speculate wildly for a moment that within the next 10-30 years or so, humanity will be able to isolate the genes that gave past geniuses their mental capabilities and to be able to augment any human brain with those genes. 

Supposedly, Einstein’s brain was preserved, whole or partial. As an aside, the story behind the autopsy of Einstein’s brain is remarkable itself. Presumably, his is not the only genius brain preserved somewhere.

Combination gene therapy treats multiple age-related diseases in mice

Towards healthy longevity! One of the implications of these stunning results is: Forecasts of the need for more medical care services and expenditures for elderly people can be relegated to the trash bin!
And this is only the beginning! We ain't seen nothing yet!

"In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases [heart failure, kidney failure, diabetes, and obesity], suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan"

"FGF21 [gene] caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFβR2 [gene] reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFβR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFβR2 could successfully treat all four age-related conditions, therefore improving health and survival"

Combination gene therapy treats multiple age-related diseases in mice: Treatment increases healthspan in mice and could lead to increased longevity therapies



Researchers able to improve, reverse age-related diseases in mice – Harvard Gazette: Wyss Institute, Harvard Medical School study offers hope for single genetic treatment for multiple age-related ills.