VDP-139 [Funding] Luminova: mtON gene therapy in the aged eye

Proposals
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VDP-139 [Funding] Luminova: mtON gene therapy in the aged eye

One-liner: Rejuvenating mitochondrial function by harnessing the power of light

Longevity Dealflow WG team

  • Senior Reviewers: Project has been evaluated by 4 reviewers: 3 academia and 1 biotech
  • Shepherd: Maria Marinova, Jason Mercurio
  • Other squad members: Eleanor Davies, Cassy Le, Adrian Matysek
  • Sourced by: Jason Mercurio

Project PI

Dr Shahaf Peleg

Simple Summary

Luminova Biotech holds exclusive rights to mtON technology, enabling mammalian cells to convert light energy into chemical energy, thus generating ATP independently of oxidative phosphorylation. This technology has improved lifespan and health in C. elegans and is effective in human and mouse cells. It offers promising applications, particularly in treating age-related human vision loss, representing a significant advancement in treating internal organs.

Problem

Aging is characterized by an increased prevalence of the cellular and molecular hallmarks of aging, which include mitochondrial dysfunction, accumulation of metabolic toxic byproducts, and systemic decline of the body vasculature. The hallmarks of aging are interconnected and a central challenge is to have a suitable and efficient treatment addressing several hallmarks at once.

Older individuals suffer from age-associated vision loss and an increased prevalence of metabolic diseases, such as diabetes, which together impair eye function (Fig 1.). Specifically, reduced oxygen transport, mitochondrial dysfunction, and accumulation of lipofuscin are involved in vision loss with aging and related maladies.

The aim for Luminova is to improve the aging phenotype with a novel approach using vision loss as an early-stage proxy. The Luminova team has developed a novel technology that can directly overcome these age-mediated dysfunctions in the eye.

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Fig 1. Prevalence of late AMD according to age and gender in Caucasians from industrialised countries

Solution

Luminova addresses the interconnected hallmarks of aging, including mitochondrial dysfunction, the accumulation of metabolic waste, and systemic decline. Recognizing the challenge of finding a treatment that addresses multiple hallmarks simultaneously, they aim to offer a comprehensive solution. The company strategically uses eye aging as an early-stage proxy for their innovative approach.

The core of Luminova’s solution is mtON technology, a novel and disruptive approach. mtON is an engineered, light-activated proton pump localized to metazoan mitochondria. This technology is designed to power mitochondrial function independently of metabolism and oxygen (Fig 2.).

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Fig 2. Mitochondria-ON (mtON) increased ∆ψm in vivo. The mitochondrial inner membrane (IM) contains the electron transport chain (ETC), which pumps protons to generate mitochondrial membrane potential (∆ψm). mtON is an engineered light-activated proton pump and, in response to light and ATR supplementation, pumps protons across the IM to generate ∆ψm

Berry, Brandon J et al. “Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan.” Nature aging vol. 3,2 (2023): 157-161. doi:10.1038/s43587-022-00340-7

The use of optogenetics to control mitochondrial membrane potential, previously demonstrated as a novel method to partially restore mitochondrial functions (Qiu et al., 2022), is a new approach for harnessing the energy of light to directly power mitochondria and sets Luminova apart in the field of aging research. This innovative approach opens a new subfield in aging research.

The company outlines a comprehensive pre-clinical trial plan in mice, focusing on the eye. This involves assessing the biodistribution of mtON, determining its functionality in isolated mitochondria, and evaluating the therapeutic benefits in the context of age-associated vision loss and diabetic retinopathy.

Opportunity

The projected longevity market is estimated to reach $270 billion by 2024, driven by a growing population experiencing vision loss. Currently, over 300 million people suffer from moderate to severe vision impairment, a number expected to increase by 50% over the next 25 years (Fig 3.). Addressing age-related vision loss presents a substantial market opportunity, and if successful, the technology could potentially be extended to address issues in other organs.

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Fig 3. Bourne, Rupert R A et al. “Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis.” The Lancet. Global health vol. 5,9 (2017): e888-e897. doi:10.1016/S2214-109X(17)30293-0

The technology developed by Luminova Biotech, known as mitochondria-ON (mtON), addresses the critical issue of mitochondrial dysfunction, which is recognized as a central factor in the aging process. The technology’s ability to optogenetically increase mitochondrial membrane potential during adulthood using a light-activated proton pump represents a groundbreaking approach with significant potential to impact aging projections (Fig 4.).

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Fig 4. Model showing effects of mtON activation in vivo. The dotted arrow represents the molecular mechanisms to be investigated that link mitochondrial membrane potential (Δψm) to aged physiology.

Here are key reasons why this technology presents a great opportunity to change aging projections:

  • The use of optogenetics to modulate mitochondrial membrane potential is a sophisticated and precise approach. Optogenetics involves using light to control cells that have been genetically modified to respond to light stimuli, providing a high level of control over cellular processes.
  • Focusing on mitochondrial membrane potential as a target is strategic, given its central role in aging. The technology directly addresses the decline in mitochondrial membrane potential associated with aging.
  • While the initial experiments were conducted in C. elegans, the ultimate goal is to translate the technology to humans. The fact that mitochondrial function is a conserved aspect across species increases the potential relevance of the findings to human aging.
  • The technology not only extends lifespan but also improves age-associated phenotypes. This implies a potential to enhance overall healthspan (Fig 5.), addressing not only longevity but also the quality of life in the later stages.

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Fig 5. mtON extended lifespan and healthspan. Light treatment began at day 1 of adulthood for all experiments. a, Survival curves of mtON-expressing animals (extrachromosomal array). Only mtON activation (+ATR +light) significantly extended lifespan, log-rank (Mantel–Cox) test, *P = 0.019. Detailed statistical information for all lifespans is presented in Supplementary Table 1. b, Survival curves of mtON-expressing animals (CRISPR insertion). mtON activation significantly extended lifespan compared to the light control by log-rank (Mantel– Cox) test, *P = 0.0001, gray and light-green curves.

Berry, Brandon J et al. “Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan.” Nature aging vol. 3,2 (2023): 157-161. doi:10.1038/s43587-022-00340-7

Luminova’s long-term vision involves upgrading mtON for functionality in inner organs. The hypothesis is that whole-body mtON gene therapy can increase human longevity. This ambitious goal positions the company to explore broader applications beyond the initial focus on eye aging.

Experimental plan and budget

MILESTONE 1: Assess the bio-distribution of mtON in the mouse eye

The team will use AAV2/9 and use two methods of injections of AVV-mtON in the eye. The team will then observe the type of cells that express mtON and confirm its mitochondrial localization. Next, the team will proceed with in vivo assessment of mtON activity functionality of mtON in isolated mitochondria. Finally, the team will determine the optimal dosage of the AVV for the next steps.

MILESTONE 2 – Assess the therapeutic benefit of mtON in the mouse eye

A) The team will test if mtON attenuates age-associated vision loss. The team will first inject AAV-mtON to the eye of old mice and test whether neuronal activity and metabolic rates of retinal cells are improved, along with vision. The team will also assess the accumulation of metabolic waste byproducts, such as lipofuscin. In parallel, the team will inject AVV-mtON in 8 months old mice to test a preventive approach and follow up with the mice until they reach old age. The team will test the benefits of mtON activation over time and measure whether less metabolic byproduct waste accumulates with time in the eye and if mtON treatment delays the onset of age-associated vision loss.

B) In parallel, the team will employ a diabetic retinopathy mouse model by injecting STZ to mice. Diabetic retinopathy is characterized by a hypoxic environment, mitochondrial dysfunction, and an accumulation of toxic byproducts and mtON treatment is an ideal gene therapy. The team will administer AAV-mtON to mice before and after STZ injection and evaluate the preventive and post-injury therapeutic potential of mtON. The team will follow similar assessments as described in section A.

Collectively, this proposal will allow the team to conduct a thorough pre-clinical trial in mice that will provide a suitable basis to move forward towards clinical trials in humans. This will also be the first critical step to translating mtON technology into humans – not only to treat aging, but to eventually explore the potential for enhancing human longevity through the integration of partially solar-powered mechanisms.

Pending successful results, we will seek funding to continue clinical trials in a timely manner.

Budget

$140,000 for two years

VitaDAO Funding Terms

This project will be funded via a Joint Development Agreement, to collaboratively develop a project. Luminova retains ownership of the intellectual property, while using IP-NFT and IPT technology for project management and governance. Funding, profits, and decision-making processes are shared, with specific conditions outlined for when Luminova regains full control of the project and how profits are distributed among token holders. Finer details will be ironed out in ongoing negotiation.

  1. Timeline

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Relevance to Longevity

This project focuses on combating age-related vision loss. Successfully treating this condition promises to significantly improve life quality for the elderly.

The ambitions of the project aims to demonstrate that the treatment, starting with the eye, could be an approach to slow down or reverse aging in the entire body since many age-related diseases are associated with mitochondrial dysfunction, the technology’s positive influence on mitochondrial health may have preventive or therapeutic implications for diseases such as cardiovascular disorders, neurodegenerative conditions, and metabolic diseases. This method uses solar energy to increase the body’s energy production, a novel and new approach that isn’t yet available on the market.

The project covers the fundamental challenges of aging: cellular senescence, mitochondrial dysfunction, accumulation of toxic waste, and systemic vascular decline.

Team

Dr. Shahaf Peleg, Project Lead

  • PhD Georg-August-UniversitĂ€t Göttingen 2010; BSc Ben Gurion University, Beer Sheva 2006
  • Tenured Group Leader at the Research-Institute for Farm Animal Biology (FBN), Dummerstof, Germany
  • Luminova Biotech, CEO

Shahaf focuses on novel approaches to extend healthy lifespan, including enabling metazoans to harness the energy of light and translate it to chemical energy in their mitochondria.

Dr. Andrew Wojtovich

  • Assoc. Prof. Department of Anesthesiology and Perioperative Medicine (SMD)
  • Assoc. Prof. Department of Pharmacology and Physiology (SMD), University of Rochester
  • Luminova Biotech, CSO

Andrew uses optogenetics to study the role of site-specific ROS production in mitochondrial physiology and hypoxic stress signalling. His work developed the mtON technology to control mitochondrial function using light.

Peter Hungerford

  • Luminova Biotech, CFO

Peter graduated from Syracuse University with a degree in Accounting and Economics and built a real estate portfolio of over 1,000 units. To date, his cumulative transaction volume is in excess of $5 billion.

Strengths

Innovative Approach: Luminova’s focuses on rejuvenating mitochondrial function through the groundbreaking use of optogenetics, presenting a novel approach to address multiple aging hallmarks simultaneously.

Exclusive Technology: Luminova Biotech holds exclusive rights to mtON technology, a light-activated proton pump engineered to enhance mitochondrial function independently of oxidative phosphorylation.

Strategic Target: Focusing on mitochondrial membrane potential as a target is strategic, given its central role in aging. The technology directly addresses the decline in mitochondrial membrane potential associated with aging, presenting a holistic solution.

Application to Aging Phenotype: The project aims to improve the aging phenotype by targeting age-related vision loss as an early-stage proxy. This strategic focus allows for comprehensive pre-clinical trials, particularly in mice, with the potential to extend to broader applications beyond the initial eye aging scope.

Ambitious Long-Term Vision: Luminova’s long-term vision involves upgrading mtON for functionality in inner organs, with the ambitious goal of whole-body mtON gene therapy to increase human longevity. This ambitious vision positions the project to explore broader applications beyond the initial focus on eye aging.

Risks

Early Stage Technology: The project’s reliance on a relatively untested method in higher organisms – using light energy for mitochondrial stimulation – is a significant risk. The effectiveness and safety of this approach in long-term human applications remain to be thoroughly validated.

Long Development Timeline: From initial research to clinical trials and technological advancements for treatment of inner organs, the timeline can span many years, if not decades. However, the application to the eye would be aided by a precedent set for gene therapy approval for eye administration.

Complexity in Treating Aging: Aging is a complex and multifactorial process. While the project aims to address several aging-related issues simultaneously, the interplay of these factors in aging is not fully understood. This complexity could pose challenges in accurately assessing the treatment’s efficacy and potential side effects.

Luminova pitch recording and transcript

Senior Review

Reviewer 1 (total score 4.1):
Overall positive. Appreciates the novelty, potential market entry due to existing therapies, and the project’s alignment with their interests in exploration and innovation. Suggests the project could benefit from additional expertise in ocular gene therapies and navigating regulatory pathways.
Concerns: Questions the technology’s maturity, specificity to certain pathophysiological mechanisms, effects on mitochondrial function beyond ATP production, and potential immune responses to foreign protein expression. Suggests further studies in other mouse models and monitoring immune activation and stress markers in response to the fungal protein.

Reviewer 2 (total score 4.5):
Overall positive. Highlights the strong team, appropriate choice of the eye for initial trials, step towards mammalian systems, and translatability to human diseases. Commends the novel mechanism and overall strategy.
Concerns: Expresses concern over the clarity and complete understanding of the mechanism, potential surprises, and believes the budget may be underestimated. Encourages contingency planning for potential setbacks.

Reviewer 3 (total score 2.8):
Positive Aspects: Acknowledges the novelty of the technology and the strong scientific team.
Concerns:
Impact on Disease Unclear: Doubts about the technology’s ability to significantly impact human disease due to unclear benefits of increased mitochondrial activation.
Complex System with Modest Results: Notes the complexity of the system and its modest increase in lifespan, questioning the translatability to viable therapy.
Lack of Drug Development Expertise: Suggests the team lacks expertise in drug development and could benefit from consulting with experts or organizations with experience in viral drug products.
Uncertain Patent Situation: Unclear about the status of patent applications related to the work.
Skepticism about Disease-Solving Capability: Questions the approach’s ability to address specific diseases like diabetic retinopathy, given the focus on increasing mitochondrial energy production without a clear mechanism for reversing eye damage.

Responses from applicant:
Lack of Drug Development Expertise:
The project team has secured expertise from Dorothea Skowronska-Krawczyk, an eye expert at UCI, to consult on the project.
They have also partnered with a CRO specializing in preclinical eye experiments, with plans already finalized and ready to proceed. This partnership is expected to supplement the core team’s capabilities effectively.

Questioning the Efficacy and Complexity of the System:
The team references the clinical validation of using optogenetics in treating eye diseases by Nanoscope Therapeutics as evidence of a viable path towards developing drug products.
They acknowledge the modest lifespan increase observed in their studies but argue that their approach is less complex for the eye, given its natural synthesis of ATR and regular exposure to light.

Concerns About the System’s Impact on Disease:
The team suggests that the perception of the effectiveness of interventions in worms versus humans may not always hold. They propose that certain interventions might show modest effects in model organisms like worms but could have significant impacts in humans, particularly for conditions like cancer where the model organism’s biology might not fully capture the therapeutic potential.
They further argue that the eye’s natural biology makes it a more straightforward system for their approach, leveraging its inherent synthesis of ATR and daily light exposure, potentially simplifying the application of their technology compared to the initial experiments in worms.

Reviewer 4 (total score: 3.8):
Overall positive. Acknowledges the project’s success in demonstrating a proof of concept in C. elegans and recognizes the significant market potential for treating age-related vision loss. They find the project’s goals reasonable and achievable within the set budget and timeline. They highlight the novelty of using optogenetics to reverse age-associated decline but remain cautious about the project’s ability to enhance health span in mammals without further clarification on the approach to achieve a light-independent system.
The main concern about the technology’s applicability beyond the eye and its dependence on light for effectiveness.

Response from applicant: There is a clear idea on how this can be done and there are studies underway on this front but cannot comment much at this point.

Bibliography

Luminova Main Papers

On improving mitochondrial functions

Visible lights reduces longevity in C.elegans

Advances in Ophthalmic Optogenetics

Optogenetics against senescence

  • Agree
  • Revisions Requested (Detail in Comments)
  • Disagree
0 voters
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The recording and transcript are behind a sign-in.

Targeting the eye seems a reasonable start, but I don’t see any eye people on the team. Is the goal to target the RPE, the macrophages, the neurons, muscles around the lens or what?

What strain of mouse will be used? IIRC, B6 and some other inbred strains have a genetic predisposition to blindness.

What cells account for the longevity phenotype in C. elegans? It’s not clear there will be any benefit to the eyes.

If there’s no change to respiration in the worms, despite an increased mitochondrial membrane potential, why is the presumption membrane potential instead of some compensatory mechanism to manage energy homeostasis in the worm? Maybe it’s lower energy demands on the mitochondria that lead to less damage. Did feeding the worms FCCP change the measured mitochondrial potential? It’s not clear how robust the phenotype is.

From a big picture standpoint, reducing energy input/increasing autophagy seems associated with longevity, but mtON should boost the amount of energy produced instead of reducing it. What about worms that get rapamycin plus the mtON/light/ATR? Is the longevity boost synergistic, additive, or no change?

Another possibility is that the mtON cells turn over more rapidly due to high membrane potential, which clears out senescent cells, and contributes to lifespan that way. This could be a major problem if it shortens the lifespan of any of these eye cells. If it targets senescent cells, not sure the eye will be the best model to start.

Why TMRE+Mitotracker Green instead of JC-1?

From an approach standpoint, not sure AAV is the best delivery vehicle. There seem to be no plans to test durability of expression, ability for repeat dosing or longevity of the transfected cells. On one hand, eyes should shut down immunity to the foreign antigen, on the other hand if you break tolerance, they’ll go blind.

It seems like there are a lot of unknowns that need to be solved first. Seems like R03 territory for me.

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Good morning and thanks for your comments.

We are supported by Dr. Dorota Skowronska-Krawczyk who is an eye expert from UCI. She is part of our team and guides us with the experimental design. We are now starting biodistribution of mtON injection in the mouse eye with the CRO Experimentica. We will also then assess the toxicity and durability expression of the mtON.

The strain of mice that we will be using is Balb/c mice.

We did not try rapamycin - an interesting idea. However, we did find additive lifespan increase with constitutively active AMPK in worms. Adding FCCP has abolished the lifespan increase by mtON.

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The recording is behind a sign-in because there were some confidential data disclosed in the pitch.
Whoever’s interested can request access which is granted if NDA is in place.
cc @gweisha

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Double checked. B6 go deaf, not blind. That was my mistake.

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hi @Shahaf this is very cool science and great work @m_marinova, @Ageless_Partners, and Squad for putting together an innovative commercialization proposal. The reasons I’m still somewhat on the fence have to do with translatability and freedom to operate.

Can you get some sense from the published literature that augmenting mitochondria in the way the mtON would be expected to do would work well for AMD? Perhaps this might help answer @bowtiedshrike’s questions about the mechanism of the longevity effects.

Also AAV seems fine for PoC mouse studies but I’d like to see the pros and cons to this vs. other arguably safer approaches such as lipid nanoparticles.

Lastly, I would think the orginators of optogenetics, because they are at well-resourced institutions, might be a barrier to your claims of having “exclusive rights”. Can you comment on how you will have and maintain freedom to operate? I don’t know the field but I imagine the original patent holders did something like what happened with CRISPR where basically anything fell under their patents.

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This is decades away. There are real animal models for this. Worms? There are AAV animal models for this that are clinically validated. There are already drugs out there. The space is crowded with next gen tech.

We cannot keep giving “grants” for good science and basic research. We need commercially viable assets. That’s what brings value to VitaDao and patients.

If we don’t start investing in commercially viable assets and IP we are going to become a research foundation that doesn’t profit or get anything approved.

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Optogenetics therapies are already in clinical trials for the eye, so this is not decades away. Whether this particular plan is the right plan is a good question, but optogenetics is a moonshot approach and many at VitaDAO have expressed interest in funding more moonshots.

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Hi Tim,

Thank you very much:)

I think overall, AMD, as well as general aging, is accompanied at least partially with oxidative stress and mitochondrial dysfunction. On top of that, the aged eye (including diabetes) have dysfunctional vascularization (so impaired oxygen supply). Factoring all these components together, we hypothesize that mtON be able to compensate for these age-associated dysfunction as part of the ATP will be supplied via the light (no oxygen, upstream metabolism and such as needed). Furthermore, because of that, we think it will reduce the metabolic stress.

I asked our eye expert in the company and the CRO we are working with regarding lipid nanoparticles, 
AAV is the way to go. There is already a company doing AVV genetic treatment for eye genetic disease (Btw, they charge an enormous amount of money per injection
). Saying that, if the tech advances, I see no problem to embrace it.

I am glad you asked about optogenetics. I don’t think mtON is classic “optogenetic” (if at all). Optogenetic was invented to control a process- switch on/off protein/process due to light sensitivity. mtON is different - it actually harnesses the energy of photos into chemical energy in our mitos. It’s an energy converter. Hence its novel, hence the patent. So we are the first ones that use the energy of light itself, to power up the mitos in the context of aging.

I hope sharing my view answered the questions - please don’t hesitate to follow up either here or next time we meet.

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I can share my view here. We are not looking for a grant. We have enough in our academic settings.

We wish to translate it into the real world. And we are seeking investors that share this vision:

We can extend our health span by giving more money to research on exercise, diet intervention, rapamycin (and other drugs), staring at red light and such. However, if we follow this path, we will never (I bet on this) manage to have a person living over 150. The only way to potentially achieve that is via more radical out of the box approaches. mtON is one such radical and disruptive idea. My interaction with VitaDaoers in recent years led me to believe that many people share this vision. Hence we applied. Its about the vision to meaningfully increase life span.

Using AAV to treat genetic disease makes, forgive my language, s**t loads of money. Imagine if our preclinical works - how much buzz this would create.

Now, the eye is the first step. We have clear idea how to approach mtON activation in inner organs.

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Tim,

Maybe we need another term for mtON. Not classic optogenetic. Is more harnessing energy optics.

Overall I dont think its decades away. If it works, theres a clear path to do it. And we are determined to do it:)

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Really excellent responses thanks @Shahaf!

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I am all for funding moonshot projects and this technology is very interesting IMO. Unfortunately, this is not a good moonshot project - it extends the lifespan in c.elegans by a little more than 30%. That means that if and when this thing gets to humans, the effect will be insignificant.

If the impact were >100% I would be happy to agree with the proposal but given the available information I vote “disagree”

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Hi Michele,

Thank you very much for sharing your view - I appreciate it! I would like to share with you my thoughts that may address your comment. It’s not in a specific order of importance.

  1. Worms aren’t the best model for optogenetic - they are usually light aversive and live in the soil. Some short wavelengths of light may even shorten lifespan. But our eyes love the light:) Also, the light LED setup may slightly increase the temperature that may also shorten a bit of life span. We tried to control it.

  2. mtON may be combined with other life span interventions. We did AMPK activation + mtON and it was additive. Although we did not make a direct comparison (will address in the next point), we ended up with control living 19-22 days medican vs 34 in mtON+ AMPK. That’s over 50% actually.

3
which brings me to optimization. There are millions of papers on diet, rapamycin and the rest. Years of optimization. mtON has two papers and we hardly optimizined anything - what light regime, how much mtON expression, how much ATR,
). Also combining with oth4er interventions
lots of potential to unlock.

  1. Still, the goal isnt to spend years making worms super long lived. We want mammals. mtOn activation leads to inmporved T-Cell function. Please refer to:

So the effect in T-cells is not ‘insignificant’ - at least based on preliminary data.

  1. And even if all I write is not too convincing (which I hope is not:) ), still 20-30% improvement (it will never be 100% anyway) of eyesight is quite great for people losing their eyesight.

  2. To be sure, we are working on upgrading the technology.

Cheers,

Shahaf

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@michele.gallia I agree with @Shahaf here. 30% effect size is the very first attempts. If you’ve done science, you know that many big phenotypes are the result of tons of trial error. Moonshots by definition are things that are extremely hard to do, so one wouldn’t expect to land on the moon on the first try.

Some super sobering context. The hottest, most well funded idea in longevity - epigenetic reprogramming - is currently at a 7% effect size. When Bezos and others had already given it $3B, it was a 0% effect size. So in this light, Shahaf is doing pretty good!

Peter Thiel famously said “competition is for losers” where the idea is:

“Additionally, Thiel argues that competition can lead to a lack of innovation, as companies are more focused on copying their competitors, rather than coming up with new ideas.”

“only companies and entities that seek to build and wield monopolies are destined for long term sustainabiliity.”

I think what’s Shahaf is doing here - inventing a new field - is what lines up with Thiel’s and VitaDAO’s philosophy.

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Thank you Tim for your contribution to the discussion.

Here are my two cents

  1. The tweet refers to a 7% effect in mice, not in worms so it is not comparable. I do not know of any therapy that has a bigger effect on mice than on worms for the simple reason that mice are much more complex than worms.

  2. Nothing that has a 30% effect on worms will translate to 20-30% in humans, NOTHING

3.Here is an example of a research with decent results in worms >100% effect, which I am sure you know. and with no upgrading, optimization, etc., from my understanding. Kenyon C - Search Results - PubMed

I agree 100% with you that we need to finance moonshot projects but unfortunately I do not think this is a good one.

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@Shahaf

Thank you Shahaf for your answers to my questions and I will make sure to read the paper you mention. Here are a few initial thoughts

  1. I would argue that worms are not the best model for any disease in humans

  2. you are proposing mTON + ATR + light + an additional therapy - the odds of having side effects look pretty big to me

  3. you mention optimization and upgrading the technology - can you elaborate on some potential avenues you are exploring without going into the details? Specifically how do the activities you mention in the timeline refer to that?

  4. Once again 20-30% in worms will never translate to 20-30% improvement in humans NEVER

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I’m aware. We are making two different points. My point is about not conflating today’s capabilities with tomorrow’s possibilities (ref). Those that invested in reprogramming and numerous other foundational technologies didn’t.

Everyone is free to think an individual plan won’t pan out. That’s why we vote😀

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I understand, and my point is:

Given today’s capabilities, tomorrow’s possibilities are bleak for this research :wink:

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Also, a way more advanced company seems to be doing something that looks very similar

GenSight Biologics, is developing a pipeline of therapies using mitochondrial targeting sequence and optogenetics technologies to address retinal diseases and central nervous system disorders.

https://www.gensight-biologics.com/clinical-development-summary/

@Shahaf what is your take on this?

And more here Light-controlled genes and neurons poised for clinical trials | Nature

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