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Call it “When Harry Potter Met Sally.” In a new romantic comedy, Daniel Radcliffe plays the nonwizardly Wallace, a medical school dropout whose heart goes kaboom for a hipster gal. The only problem is that she already has a boyfriend. The film, “What If,” then explores a question: Can two people with clear chemistry just be best friends?

“What If,” now showing locally and co-starring Zoe Kazan and Adam Driver (HBO’s “Girls”), does not attempt a wholesale reinvention of the troubled romantic comedy genre. But the movie also represents an effort by independent films not to give up on it, either, the way the big studios have. Instead, a smattering of aspiring young directors and writers is taking the form and tinkering, twisting and turning it inside out to instill freshness.

“People are not tired of romantic comedies,” Radcliffe said in a telephone interview. “They are tired of manipulative, cheap and sappy films filled with big romantic gestures that never happen in real life, ever.”

Consider the batch of quirky rom-coms joining the generally well-reviewed “What If” in theaters soon. “Life After Beth” tries to shake up the genre by adding some light horror; the girlfriend, played by Aubrey Plaza, turns out to be a zombie. “The One I Love” pairs Mark Duplass and Elisabeth Moss as a married couple experiencing a highly unusual, almost supernatural weekend getaway. (To say more would be a spoiler.) “Two Night Stand” is the directing debut of Max Nichols – the son of Mike Nichols – and tells the story of a quick romp extended by a freak snowstorm.

Also new are “They Came Together,” an Amy Poehler-Paul Rudd spoof of romantic comedy clichés, and “Obvious Child,” a comedic romance that centers on, of all things, an abortion. Coming this fall is Lynne Shelton’s “Laggies,” which finds the woman (Keira Knightley) and not the man stuck in permanent adolescence.

This crush of small-budget romantic comedies is no accident. Independent filmmakers and distributors have spotted a marketplace void. The big studios, scarred by flops like “How Do You Know” and “Confessions of a Shopaholic,” are retreating from this genre. They have released only one full-fledged rom-com this year: “Blended,” from Warner Bros., a $45 million dud co-starring Adam Sandler and Drew Barrymore.

But in indie land, where movies are produced for as little as a few hundred thousand dollars, even modest ticket sales can be a home run. A distribution company focused on young and arty viewers, A24 Films, is doing cartwheels over the response to “Obvious Child,” an R-rated film that makes light of a third-rail subject. An “abortion comedy,” it has taken in about $3 million since arriving in late June. It cost about $500,000 to make.

“These films work when they are honest,” said David Fenkel, a founder of A24, which will release the similarly R-rated “Laggies” in October. “You can’t grind down the edges in a crass attempt to get a PG-13 and broaden the audience.” Put another way, A24 and the other tiny distributors taking on these films – despite some of the stars involved – are not in the mass appeal, dumb-it-down business.

The surest way to make an honest romantic comedy? Don’t rely on men to make it, the way endless studio efforts have. “It’s notable that both ‘Obvious Child’ and ‘Laggies’ are female-written, female-directed films about female stories that star females,” Fenkel said, adding, “Duh.”

All of these new romantic comedies work hard to avoid formulas that have had success in the past but became so overused that audiences started to roll their eyes: the reformed playboy (“50 First Dates”), the race to the airport (“How to Lose a Guy in 10 Days”), the bickering love birds (“You’ve Got Mail”), the career woman in a ridiculous romantic circumstance (“The Proposal”). Radcliffe said he was drawn to “What If” partly because it rejects the grand romantic gesture. (See: airport, running through.) For instance, when Wallace, Radcliffe’s character, flies to Ireland at the spur of the moment to profess his love for the vacationing Chantry (Kazan), she responds not with a gooey embrace but with outrage.

“There’s something that’s so refreshingly real about that response,” Radcliffe said. “It’s not romantic to stalk someone across an ocean. It’s creepy.”

Some of these films experiment more than others. “Life After Beth,” which was first noticed at the Sundance Film Festival in January, moves from happy, funny and romantic to odd and macabre. Toward the end, Plaza’s zombie eats her father. Meanwhile, “What If,” acquired by CBS Films for less than $2 million at last year’s Toronto International Film Festival, features a performance by Radcliffe that is reminiscent of Hugh Grant’s in old hits like “Notting Hill” and “Bridget Jones’s Diary.”

“You know – a little nebbish, a little bit awkward, likable in his self-deprecation,” Radcliffe said. (And British.)

The romantic comedy and its problems have received a lot of attention lately, partly because there have been so few successful ones and partly because July was the 25th anniversary of the seminal “When Harry Met Sally.” In a series of articles devoted to the genre last month, Grantland.com wondered in a headline, “Have Romantic Comedies Become Obsolete?”

For this group of filmmakers, the answer seems to be a resounding “No.”

“I saw it as a massive opportunity,” said Michael Dowse, who directed “What If.” “Romantic comedy allowed me to flex a different muscle as a director,” he said. “And if you nail the genre – if you keep it simple and honest and don’t overcomplicate it – you can create something timeless.”