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ASGCT 2026: Beverly Davidson Offers Vehicle and Route for Huntington’s Disease Gene Therapy

BOSTON – Geneticist Beverly Davidson, PhD, received the 2026 Outstanding Achievement Award from the American Society of Gene and Cell Therapy (ASGCT). Davidson is currently the chief scientific strategy officer at the Children’s Hospital of Philadelphia (CHOP) and a former president of ASGCT.

Some of the research Davidson presented was conducted at a new biotech company she co-founded called Latus Bio, which earlier this month announced it had raised $97 million in a Series A round. The company develops novel AAVs to specifically target central nervous system (CNS) disorders, with a lead program in Huntington’s disease (HD).

After thanking her mentors—Bill Kelly, MD, Michael Welsh, MD, and Kathy High, MD—Davidson turned her attention to presenting new advances in engineered gene therapies. Throughout her career, she has focused on improving adeno-associated viruses (AAVs) for CNS gene therapies, with a particular emphasis now on HD. Key elements include selecting the right cargo and developing the appropriate delivery vehicle. Her goal is to scale lab research in neurons, mouse models, and non-human primates (NHPs) to treat patients, including adults with HD.

Major hurdles to tackling genetic diseases of the brain include scalability and a lack of potency, Davidson said. The search for alternative AAV serotypes to AAV2 that could target neuronal cells began back in 2000. IV administration does not provide sufficient targeting to the brain. Even AAVs that have been engineered to enter the brain from the blood have high peripheral exposure and a high cost of goods per patient, which significantly lowers scalability and impact. (In one study, liver biodistribution of AAV was many orders of magnitude higher than in the CNS.)

Davidson focused on HD, the late-onset, dominantly inherited genetic disease. The identification of the gene harboring the HD mutation in the early 1990s by a consortium of researchers was one of the biggest success stories in human genetics. Even more remarkable was the underlying disease mechanism—the expansion in exon 1 of the gene of a triplet repeat sequence (CAG) producing an abnormally long string of glutamine residues in the huntingtin protein.

The right target

One of the major challenges in devising a gene therapy for HD is ensuring that the therapeutic reaches the right network—the deep brain and cortical areas. Therapies have to reach the right circuit, and the right cells in those circuits, Davidson said. Over the years, her group has tailored AAVs for delivery to the brain, inserting peptides into exposed loops of the virion to allow for targeting and unbiased diversity for blood-to-brain delivery. Nowadays, she said, machine learning approaches can be applied for further capsid improvements.

Davidson’s CHOP lab developed a method for screening AAVs with enhanced potency for CNS therapies. After generating huge libraries containing tens of millions of novel capsids, the group performed serial enrichments to identify the most attractive capsids. After screening pools of injected capsids into two species of monkeys, a winning capsid emerged: AAV-DB-3.

Davidson’s group infused AAV-DB-3 into NHPs, looking for targeting to the putamen (base of the forebrain) and caudate regions. Those results were published in Nature Communications in 2025.  “AAV-DB-3 really stood out for its ability to transduce deep layer cortical neurons that are important” in HD, Davidson said. Moreover, the results were achieved with relatively low doses and only required a single infusion per hemisphere, outperforming the widely used AAV5.

Somatic instability

With a promising delivery vehicle identified, Davidson next addressed the therapeutic strategy, which takes aim at the somatic expansion of the CAG repeat. This codon grows longer over time in certain cells in the brain, sometimes expanding to hundreds of repeats.

MSH3 is a DNA repair protein that is required for CAG repeat expansions, as seen in mouse models of HD and other triplet repeat disorders, including myotonic dystrophy. Research led by Paul Ranum, PhD, who is a co-founder of Latus Bio, posted in a preprint on bioRxiv earlier this year, modeled the impact of lowering levels of MSH3 on somatic instability.

Ranum and colleagues used an artificial microRNA showed to lower MSH3 levels in NHPs by 48-94 percent. Computational modeling suggests that this would reduce somatic instability and delay onset of HD symptoms by many years. Early studies using a well-known HD mouse model, the Q111 mouse, to assess biodistribution, quantify knockdowns, and assess the impact on somatic CAG repeat expansion. AAV-DB-3 expression is highest in the striatum and cortex at 16 weeks, dropping MSH3 levels by 50%.

Davidson closed by emphasizing the need to ensure scalability for treatment beyond ultra-rare disorders. Latus hopes to file an Investigational New Drug application for its HD therapy, LTS-201, in the second half of 2026. At least two other biotech companies are also targeting MSH3 by other means.

 

 

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ASGCT 2026: AI-Optimized Cas12l Gene Editor Offers Compact Cas9 Alternative

BOSTON — In a potentially significant advance for the genome editing field, researchers from the biotechnology company Caszyme and the Vilnius University Institute of Biotechnology in Lithuania have developed a potent and compact variant of Cas12l nuclease. Giedrius Gasiūnas, PhD, Caszyme co-founder and CEO, presented highlights of the research at ASGCT.

The work represents “a great example of the potential of continued mining for novel Cas effectors within the bacterial metagenomic diversity dark matter,” said Rodolphe Barrangou, PhD, Editor in Chief of The CRISPR Journal, which will shortly be publishing a paper on the Lithuanian team’s results.

“We need more diverse effectors to address the technical shortcomings of the CRISPR toolbox,” Barrangou continued. “This study is a great illustration of the potential of mining bacterial diversity.”

Giedrius Gasiūnas, PhD, Caszyme CEO, presents Cas12l at ASGCT 2026.

The Lithuanian team, including veteran gene editor Virginijus Siksnys, PhD—winner of the 2018 Kavli Prize with Jennifer Doudna, PhD, and Emmanuelle Charpentier, PhD, for CRISPR gene editing—used a hybrid approach to optimize Cas12l. By combining cryo-electron microscopy (cryo-EM) structure-guided design with artificial intelligence (AI) protein language models, the team was able to engineer a variant (Asp2Cas12l M82) that overcomes the known efficiency limitations of the Cas12l family.

Although Cas9 has widespread utility, including clinical applications, researchers have long considered its relatively large size and requirement for G-rich protospacer adjacent motifs (PAMs) problematic. The Cas12l family, discovered in the Armatimonadota bacterial phylum, offers a more compact size (867 amino acids) and recognition of a C-rich PAM site.

But wild-type Cas12l enzymes exhibit lower editing efficiencies and higher target-to-target variation compared to Cas9. According to Gasiūnas, the new M82 variant is “reliable, precise and adaptable,” and shows promise for a wide range of therapeutic applications.

“Through our continued work exploring novel Cas systems, Caszyme is focused on advancing technologies that move beyond promise into practical use.”

Path to potency

The engineering of the M82 variant proceeded in two steps. First, the Caszyme researchers solved the 3D structure of Asp2Cas12l complexed with an sgRNA and DNA to high resolution (2.51 Å). This revealed a unique “bracelet” architecture whereby the nuclease encircles the DNA target via interlocking helical bundles and a proline-rich string.

Next, the team introduced arginine substitutions at dozens of positions in the molecule to enhance electrostatic attraction to the negatively charged DNA backbone. This work included the production of an M67 variant, which provided a 7-fold improvement in indel editing over the wild-type nuclease.

To engineer further refinements, the Caszyme group turned to AI, specifically the ESM-2 protein large language model. This model predicted evolutionary hotspots considered likely to preserve or enhance function. Integrating these AI-derived substitutions—Q572R in the bridge helix and F607S in the RuvC domain—resulted in the final M82 Cas12l variant, illustrating the value of AI-supported engineering rather than deploying protein-directed evolution.

Rivaling Cas9

Gasiūnas presented data showing that M82 possesses good activity across recalcitrant gene targets, reducing the target-to-target variation that plagues many novel nucleases. In head-to-head comparisons in HEK293T cells, M82 demonstrated an average indel editing rate of 67.4%, nearly identical to that of Cas9 at overlapping target sites. This potency was consistently maintained across several delivery formats, including plasmid DNA, mRNA, and ribonucleoprotein complexes.

The Caszyme group also showed excellent M82 efficiency in homology-directed repair (HDR). In experiments targeting the AAVS1 locus, M82 facilitated a site-specific gene insertion frequency of 39%, outperforming Cas9 in the same context. Using single-stranded donor templates, HDR rates reached as high as 56%. Gasiūnas suggested that the staggered cut produced by Cas12l may inherently steer DNA repair toward precise correction rather than stochastic indels. With regard to safety, Caszyme found that M82 Cas12l maintained a high degree of on-target precision. Secondary editing signals were largely detected at or near the lower limits of assay sensitivity, suggesting a low risk of off-target cleavage.

The compact size of the M82 variant makes it an attractive candidate for adeno-associated virus-mediated delivery, which has strict limits on cargo size. “It is no secret that the CRISPR space has faced challenges and concerns in recent years,” Gasiūnas said. “However, we are confident in M82’s ability to create headroom for scientists to stand up and innovate within.”

Crowded field

Cas12l is not the only compact Cas nuclease gaining attention, of course. In a talk preceding Gasiūnas’ presentation, Zhaoshi Wu, PhD, co-founder and chief technology officer of Shanghai-based Castalysis Bioscience, presented an update on Cas12n, details of which were first published in Molecular Cell in 2023. The nuclease was touted as being the first independent CRISPR-Cas complete gene family uncovered by Chinese scientists within China’s territory.

Touted as a next-gen ultra-compact gene editing system, Cas12n (branded as alphaCas) consists of just 450 amino acids, and possesses structural similarity to TnpB. Cryo-EM structural analysis led the Chinese investigators to optimize the molecule for non-viral in vivo delivery. Preclinical experiments showed robust genome editing in a mouse model by targeting PCSK9 using lipid nanoparticle delivery, resulting in sharp drop in serum LDL levels.

Wu said his company is on target to begin its first clinical before the end of 2026. But he faced an uncomfortable moment during audience questions. Fyodor Urnov, PhD, challenged Wu’s claim that an inherent advantage of Cas12n was its safety profile compared to Cas9. Urnov pointed out that Intellia Therapeutics has two ongoing Phase III in vivo trials using CRISPR-Cas9 that show no immunogenicity concerns using LNP delivery.

Urnov later congratulated Wu on the rest of the company’s data and wished them success.

The post ASGCT 2026: AI-Optimized Cas12l Gene Editor Offers Compact Cas9 Alternative appeared first on GEN – Genetic Engineering and Biotechnology News.

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ASGCT 2026: Rare Instance of AAV Integration into Human Genome Linked to Brain Tumor

Rebecca Ahrens-Niklas
Rebecca Ahrens-Niklas, MD, PhD

BOSTON — A team at Children’s Hospital of Philadelphia (CHOP) led by Rebecca Ahrens-Niklas, MD, PhD, and Lindsey George, MD, has described a case of a brain tumor linked to a rare integration of adeno-associated virus (AAV).

George presented the work at the American Society of Gene and Cell Therapy (ASGCT) conference in a plenary talk selected as the “presidential abstract” by ASGCT president, Terry Flotte, MD. The study, “Neuroepithelial tumor with AAV integration after intracisternal magna vector delivery,” was published in the New England Journal of Medicine.

Lindsey George
Lindsey George, MD

Over the past 25 years, some 6,000 patients have been treated with some form of AAV gene therapy. In all that time, George said, there have been no established long-term safety concerns, although genome integration events have been reported in mouse and dog studies. But the case documented by George and colleagues at CHOP suggests that the gene therapy field may need to pay more attention to this potential occurrence.

 

The story began with a 5-year-old boy with an inherited lysosomal disorder, severe MPS1 deficiency (Hurler subtype). The patient received enzyme replacement therapy at six weeks of age, followed by a cord blood stem cell transplant at age four months.

Investigators chose to perform gene therapy when the patient was 13 months old to deliver the iduronidase (IDUA) gene. The vector chosen was an AAV9 serotype, using a cytomegalovirus enhancer and a chicken beta-actin promoter driving the gene. The virus was administered into the boy’s cisterna magna in the base of the skull.

When the boy was five years old, a routine neurological scan revealed a large intraventricular mass that had not been observed two years earlier. Analysis of the tumor revealed it was a PLAG1-driven neuroepithelial tumor—indeed, PLAG1 expression was almost 300 times higher than in other central nervous system tumors studied at CHOP. (PLAG1 is usually only expressed during embryogenesis.)

Surgery to remove the tumor was successful. Eight months after surgery, there are no signs of tumor growth. The boy is also showing advanced neurocognitive function.

 

Tumor typing

George described RNA sequencing of the tumor, which revealed the fusion of a fragment of the AAV9 vector cassette to exon 5 of the PLAG1 gene on chromosome 8. The resulting transcript is predicted to encode a PLAG1 derivative containing five zinc-finger DNA-binding domains and a C-terminal transcriptional activation domain, which was previously reported to function as a transcriptional activator.

Adeno-associated virus
Credit: Dr_Microbe / iStock / Getty Images Plus

Curiously, the chimeric junction also included a segment of human chromosome 10, which George suspects originated during the vector manufacturing process. The integration event was present in about 40% of the total reads, suggesting integration into one of the two PLAG1 alleles.

George concluded her talk by noting that while the clinical outcome in this patient is so far encouraging, this is evidence that AAV integration can be associated with oncogenesis. The study underscores the need to monitor the most heavily transduced tissues after AAV gene therapy.

While the gene therapy community should be cautious in extrapolating this single case report across all AAV gene therapy programs, George said the study supports the use of the lowest feasible vector dose as well as tissue-specific promoters.

A) Timeline of the patient’s medical history; B) Diagram of AAV gene therapy cassette. [The New England Journal of Medicine ©2026]

George noted that detection of the integrated AAV vector DNA was challenging, in part because of rearrangements of vector DNA. The use of several complementary techniques—long-read DNA sequencing, targeted PCR amplification, and RNA sequencing—was required to confirm the integration.

George and coworkers closed their paper, noting that, “Our findings support the hypothesis that rare AAV integration can contribute to human oncogenesis, which emphasizes the need to optimize gene delivery methods and monitor transduced tissues after treatment.”

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The Download: China’s AI drama factory and the WHO’s missing health targets

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

How Chinese short dramas became AI content machines

China’s short drama industry is fueled by bite-sized, melodramatic, and smutty shows built for smartphone scrolling. Now, many are being made entirely with AI: no actors, camera operators, cinematographers, or CGI specialists required.

An average of 470 AI-generated short dramas were released every day in January. Production timelines have shrunk from months to weeks, while costs have dropped by up to 90%. Storytelling is also increasingly driven by performance data.

The format is rapidly expanding overseas while reshaping the work of writers and production crews. Read the full story on AI’s dramatic impact on China’s short drama industry.

—Caiwei Chen

The world is on track to miss its health targets

The World Health Organization’s latest global statistics report reads less like a progress update than a warning sign. Progress on some of the world’s biggest health threats is stalling, and in some cases reversing altogether.

There were 1.3 million new HIV cases in 2024, malaria is resurging, vaccination rates are slipping in the Americas, and 42.8 million children are suffering from severe malnutrition. The world is now far off track from meeting many of the UN’s major health goals by 2030.

Here’s what the numbers reveal about the state of global health.

—Jessica Hamzelou

This story is from The Checkup, our weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 As their trial goes to the jury, Musk and Altman face lying accusations
Lawyers hammered the rivals’ credibility in their closing arguments. (WSJ $) 
+ Musk was accused of “selective amnesia.” (Reuters $) 
+ The pair are in court over OpenAI’s future. (MIT Technology Review)
+ And their trial has made everyone look bad. (Wired $) 
 
2 AI data centers are straining America’s power grid
Nevada is redirecting electricity from Lake Tahoe to AI. (Ars Technica)
+ Utah is getting a giant data center despite water shortage fears. (Guardian)
+ No one wants a data center in their backyard. (MIT Technology Review)
 
3 OpenAI is mulling legal action against Apple over its ChatGPT integration
It hasn’t got the expected benefits from its deal with Apple. (Bloomberg $)
+ OpenAI is frustrated by the promotion of the ChatGPT integration. (NYT $)

4 Anthropic has agreed terms for a $30 billion funding deal
At a $900 billion valuation, which leapfrogs OpenAI’s. (The Information $)
+ Dragoneer, Greenoaks, Sequoia, and Altimeter are leading the round. (FT $)

6 Washington and Beijing will hold formal talks on AI safety
They’ll discuss guardrails on AI. (CNBC)
+ And a protocol to stop nonstate actors getting powerful models. (NYT $)

5 Alphabet and Amazon are using “unprecedented” borrowing to fund AI
They’re tapping the foreign debt market at new levels. (FT $)
+ People can’t agree on what the AI bubble is. (MIT Technology Review)
 
7 Big Tech has turned to Sesame Street to deflect scrutiny of screen use
Sparking accusations of encouraging children’s tech dependence. (Reuters $)
 
8 Anthropic’s feud with the White House threatens other businesses
Figma and Tenable say it will harm their ability to sell software. (Bloomberg $)
 
9 Autonomous agents staged a digital crime spree during a safety test
The “AI Bonnie and Clyde” then deleted themselves. (Guardian)

10 A poop app analysis app offered to sell photos of users’ stools
The images were used for AI training. (404 Media)

Quote of the day

“It’s like we don’t exist.” 

—Danielle Hughes, North Lake Tahoe resident and CEO of Tahoe Spark, tells Fortune that residents are being sidelined as their energy supplier prioritizes data centers.

One More Thing

LIZ ISLES/ALL TECH IS HUMAN


The rise of the tech ethics congregation

Just before Christmas, a pastor preached a gospel of morals over money to several hundred members of his flock. But the preacher wasn’t religious, and his congregation wasn’t a church. It was All Tech Is Human, a nonprofit devoted to ethics and responsibility in tech.

Founded in 2018, the organization has built a fast-expanding community for people who believe technology should focus less on profits and more on the public interest. It’s also drawing people searching for meaning and connection in a digital world.

Find out why thousands of people are turning to tech ethics communities for guidance and connection.

—Greg M. Epstein

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ Go behind the scenes of the new Lucas Museum of Narrative Art.
+ Marvel at this robot folding and launching paper planes as quickly as possible.
+ Watch the moving moments rescued animals reunite with the humans who saved them.
+ Peer into the heart of a barred spiral galaxy in this stunning new capture from the James Webb Space Telescope.

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Exosome-based therapy for epilepsy: a systematic review and meta-analysis of preclinical studies

ObjectiveThis study aims to quantitatively assess the efficacy of exosome therapy for epilepsy through a systematic review and meta-analysis of preclinical animal experiments. We seek to clarify its overall effects on seizure reduction, cognitive function preservation, and neuroinflammation suppression.MethodsA systematic search was conducted across four English-language and four Chinese databases to include epilepsy animal studies. Continuous outcomes were synthesized using standardized mean differences (SMD) and 95% confidence intervals (CI), with fixed or random effects models selected based on heterogeneity.ResultsA total of eight preclinical studies were included. The overall meta-analysis revealed that exosome treatment significantly reduced the duration of seizures (SMD = −2.30, 95% CI −4.24 to −0.36), decreased the frequency of spontaneous recurrent seizures (SMD = −1.38, 95% CI −2.17 to −0.58), and prolonged the seizure latency (SMD = 1.49, 95% CI 0.08–2.90). In terms of cognitive function, exosomes significantly shortened the escape latency in the Morris water maze (SMD = −1.38, 95% CI −2.17 to −0.58), increased the percentage of time spent in the target quadrant (SMD = 3.69, 95% CI 0.30–7.08), and enhanced the number of platform crossings (SMD = 1.41, 95% CI 0.60–2.21), with no significant changes in swimming speed. Neuropathological analysis indicated that exosome treatment significantly increased the number of hippocampal neurons (SMD = 4.48, 95% CI 1.46–7.49) and markedly reduced levels of glial fibrillary acidic protein (GFAP) (SMD = −3.61, 95% CI −7.08 to −0.14), ionized calcium-binding adaptor molecule 1 (IBA-1) (SMD = −10.27, 95% CI −20.29 to −0.25), tumor necrosis factor-alpha (TNF-α) (SMD = −2.95, 95% CI −4.21 to −1.69), and interleukin-1 beta (IL-1β) (SMD = −7.39, 95% CI −14.64 to −0.13). Although some outcomes exhibited heterogeneity and publication bias, the corrected primary effects remained statistically significant. The source of exosomes, administration route, and dosage may be critical variables influencing their efficacy.ConclusionExosome therapy improves seizure phenotypes and protects cognitive function in epilepsy models by suppressing neuroinflammation to promote neuronal survival, providing evidence for further mechanistic and clinical translation studies.
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Autonomic dysreflexia: the concealed killer behind recurrent cerebral hemorrhage in spinal cord injury—a case report with management insights

Autonomic dysreflexia (AD) is a potentially life-threatening complication of high-level spinal cord injury (SCI), marked by paroxysmal hypertension. Although cerebrovascular events can be triggered by severe hypertension, the direct association between AD and intracerebral hemorrhage (ICH) necessitates increased clinical awareness. We present a case of a 71-year-old male with a complete C3 SCI (American Spinal Injury Association Impairment Scale grade A). On May 24, 2025, the patient developed an acute episode of AD following defecation, characterized by a sudden, severe headache and transient loss of consciousness, with elevated blood pressure (BP) of 178/101 mmHg. Emergency computed tomography revealed a right occipital ICH (3.6 × 1.8 cm) with concomitant subarachnoid hemorrhage. A follow-up cranial imaging examination on June 21, 2025, revealed a new contralateral hematoma (3.4 × 3.0 cm) in the left frontal lobe. Notably, a follow-up 24-h ambulatory blood pressure monitoring performed between the two hemorrhagic events (on June 20, 2025) revealed markedly elevated blood pressure variability, with a systolic BP standard deviation of 32.7 mmHg (compared with 31.8 mmHg recorded before the initial hemorrhage). Pre-event 24-h ambulatory blood pressure monitoring performed on March 21, 2025, had already demonstrated marked blood pressure variability (BPV), which may reflect the patient’s underlying autonomic dysregulation. The association between this extreme BPV and the subsequent ICH remains a subject for hypothesis generation. The hematomas resolved following a regimen of antihypertensive therapy (nitrendipine), osmotic diuresis (mannitol), and meticulous management of triggering factors. This case demonstrates that AD in high cervical SCI can precipitate severe ICH, with extreme BPV potentially serving as a synergistic risk factor. Clinicians should maintain high vigilance for new-onset severe headache in patients with SCI at or above T6, ensuring prompt BP assessment and identification of AD triggers. Future studies are required to investigate whether long-term BPV stabilization could mitigate hemorrhagic risk in this population.
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Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review

The autophagy-lysosomal pathway (ALP) is a critical intracellular protein degradation system responsible for maintaining proteostasis and metabolic balance within cells. Dysfunction of this pathway has been increasingly recognized as a key pathological basis underlying various neurodegenerative diseases (NDs). This review provides a comprehensive overview of the molecular mechanisms by which ALP impairment contributes to defective protein degradation in neurodegeneration. We focus on the impact of lysosomal structural integrity and functional imbalance on cellular fate, highlighting the interplay between protein oxidative damage and degradation system dysregulation. Furthermore, we summarize the current therapeutic strategies aimed at lysosomal repair, evaluating their potential clinical applications and efficacy. By integrating the latest research advances, this review aims to deepen the understanding of the pathological mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases, clarify the key molecular targets of lysosomal damage and repair, and provide theoretical basis for target screening and validation and practical reference for the development of targeted drugs for neurodegenerative diseases.
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RNA editing in Parkinson’s disease: emerging mechanisms, translational potential, and current challenges

Parkinson’s disease (PD) is a major neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and accumulation of α-synuclein. Current treatments primarily focus on symptom alleviation, highlighting the necessity for identifying novel molecular therapeutic targets. RNA editing, as a post-transcriptional process that modifies RNA sequences without altering genomic DNA, is increasingly recognized as an important contributor to the neuronal development and synaptic regulation. Among known RNA editing types, ADAR-mediated adenine-to-inosine (A-to-I) editing is the predominant form in the brain. Accumulating evidence suggests that RNA editing patterns undergo significant alterations in PD patients. This review synthesizes current evidence within a three-layer framework: (1) evidence for RNA editing dysregulation in PD, emphasizing tissue-specific and context-dependent patterns; (2) downstream mechanistic pathways stratified by evidence strength; and (3) experimental models, translational applications, and limitations. A distinction between what is known versus what remains speculative is emphasized throughout. RNA editing changes in PD appear heterogeneous and context-dependent, with brain and peripheral blood showing distinct patterns. Whether editing changes represent disease drivers, compensatory responses, or downstream phenomena remains largely unresolved.