After an irreversible transition to a blissful existence with boundless cognitive, physical and transcendental euphoria, what would you do?

A chrysalis has limited insight into the nature of life as a butterfly. The metamorphosis you propose is more profound. Even so, intelligent bliss differs from being "blissed out". Therefore let's assume that life based on information-sensitive gradients of bliss also enhances our motivation to act and our sense of social responsibility.

What next?

If there still exists the slightest distress in even the humblest marine invertebrate, then intelligent moral agents aren’t entitled to rest (cf. genetically designing a happy biosphere). Even after we’ve reprogrammed the biosphere to eliminate experience below “hedonic zero”, we mustn’t risk abandoning ourselves prematurely to escapism, i.e. “hedonism” in the baser sense. Ethically speaking, mankind needs to discover the theoretical upper bounds to intelligent moral agency in the cosmos. What are our ultimate cosmological responsibilities? Perhaps the “thermodynamic miracle” (Eric Drexler) of life’s genesis means that cosmic rescue missions are impossible or redundant. We may well be alone in our Hubble volume. If so, we don't yet know this.

However, let us assume that all our cosmological duties have been discharged. Nothing exists in our forward light-cone beyond life animated by gradients of intelligent bliss.

What would I do personally?

1) I’d explore psychedelia.

Mapping out the boundaries of one's personal ignorance of the varieties of conscious experience is dauntingly difficult. Compare how even lucid dreamers (cf. I can control a computer with my mind – from inside a dream) have only limited insight into the nature of dreaming consciousness – of what it means to be “asleep”, let alone to be “awake”. Likewise, each of us while awake has only limited insight “from the inside” into what we’re lacking and into the nature of ordinary waking consciousness itself. What humans naively call ordinary waking consciousness is just one small state-space of experience among billions of state-spaces. A Mendeleev table for state-spaces of qualia is a distant prospect (cf. Qualia Computing). In what God-like state of mind could it ever be surveyed? Until then, we’re as knowledgeable as earthworms - to a good approximation at any rate.

The remedy for such ignorance might seem self-evident. Use the experimental method! Sadly, most dark Darwinian minds are not robust enough to explore the wilder shores of psychedelia, let alone cope with the alien state-spaces of experience opened up by tomorrow’s CRISPR genome-editing. Heaven knows what outlandish state-spaces of psychedelia can be generated with novel genes, alleles and exotic gene-expression profiles. Such “unknown unknowns” needn’t scare us. Granted the biology of invincible well-being that you propose, we could all safely become psychonauts. Mastery of our reward circuitry can make “bad trips” on novel designer drugs not just physiologically impossible but also literally inconceivable.

Lest all this sound too breathless, IMO we shouldn’t imagine that taking psychedelics is the route to instant wisdom – even when it’s safe for us all to become psychedelic investigators. By analogy, imagine a primitive savage who stumbles across a TV with hundreds of different channels. Alas, the TV set is faulty. The channels display only “noise”. Likewise, most physically possible state-spaces of experience have never been recruited by natural selection for any information-signalling purpose in living organisms - let alone shared in common by language-users to allow intelligent communication about their properties. Taking psychedelics today typically leads to psychosis or “enlightenment” rather than far-reaching discoveries that stand the test of time. By analogy again, a congenitally blind child who is surgically given the gift of sight is “enlightened”. Wow! (S)he is also bewildered. Mature visual intelligence takes years, if not decades, to acquire. The same is true of navigating alien state-spaces of consciousness.

Despite these caveats, I think life based on gradients of genetically preprogrammed bliss will lead to a true cognitive revolution - a post-Galilean science of consciousness.

2) I’d aim higher.

Darwinian consciousness is polluted by misery and malaise. By contrast, the biology of lifelong well-being you propose seems almost magical. Yet why stop there? Strip away the considerations of prudence and morality that constrain our personal exploration of pleasure today (“Pleasure is the greatest incentive to evil.” - Plato). Artificial intelligence and genome-editing promise to make such practical problems soluble. Empirically, for reasons we don’t understand, there is an intimate link between pleasure and value. The experience of lifelong superhuman pleasure will yield the experience of lifelong superhuman value too. Biotech can make everyday life sublime.

The following example may seem homely. I hope it nonetheless makes the point. If like me you star your music collection from 1 to 5 for excellence, then a music collection that yielded a star-rating of 6 to 10 would induce tingles down your spine all day. What if our reward circuitry could be redesigned to yield a default hedonic range of 95 to 100? Critical discernment could be retained (cf. An information-theoretic perspective on life in Heaven). Yet our musical pleasure and capacity for musical appreciation would be out of this world. Today we don’t know what we’re missing. The same holds for art, beauty, sexuality, introspection, spirituality – and personal relationships (cf. Ecstasy : Utopian Pharmacology).

Trapped in the squalor of Darwinian life, most of us find the prospect of such an elevated hedonic range is fantastical at best. Yet neuroscientists are already homing in on the molecular signature of pure bliss in our twin “hedonic hotspots” in the CNS (cf. Building a neuroscience of pleasure and well-being). In principle, we can amplify subjective well-being by orders of magnitude beyond today’s “peak experiences” (cf. Superhappiness ?). Artificial intelligence researchers sometimes speculate on a future of recursively self-improving software-based AI that bootstraps itself to full-spectrum superintelligence (cf. Intelligence explosion - Wikipedia). Why not create recursively self-improving happiness too? Rational value-maximisers, at least, should aim for an analogue of Moore’s law that embraces recursively self-improving subjective well-being.

Right now, yes, the molecular biology of such hedonic enrichment seems a utopian pipedream. I think our overriding ethical focus should be on mitigating, preventing and eventually abolishing outright the biology of suffering. Human civilisation is based on the exploitation and abuse of sentient beings (cf. Industrial farming is one of the worst crimes in history). Talk of creating a living world based on gradients of superhuman well-being rings hollow (cf. Speciesism: Why It Is Wrong and the Implications of Rejecting It - Kindle edition by Magnus Vinding. Politics & Social Sciences Kindle eBooks @ Amazon.com.). But coming into existence needn't be harmful indefinitely (cf. the harm of coming into existence by David Benatar). Mastery of the molecular machinery of bliss promises an exponential growth in intelligent well-being - a major evolutionary transition in the development of life.

Transhumanists believe we should be working for a “triple S” civilisation of superintelligence, superlongevity, and superhappiness.
The welcome gift of personal bliss wouldn’t (I hope) change this goal.